The series has been compared to Batman: The Dark Knight Returns, a comparison which Marvel has also quoted when promoting Reign. As well as the thematic similarities between the two stories, both of which revisit aged heroes after the end of their careers, The Dark Knight Returns is also acknowledged within the pages of Reign by the inclusion of a character named Miller Janson (the name reflects Dark Knight Returns creators Frank Miller and Klaus Janson).
The book also has several themes relevant in the post 9/11 world, most notably Mayor Waters taking control of the city of New York to protect it, and the WEBB, an energy field that seals all of New York inside it so no one can leave. Also, security levels, such as orange and yellow, appear during the storyline.
This is a story that runs parallel to continuity. It's an option. It's an opinion. This is me taking a world I love, taking the characters I love and making them hurt. I want to be very clear that this is not an alternate reality. This is my reality and I invite you all to explore it with me. At one point in my life, my whole existence was Spider-Man. Now, for a little while at least it's true again.- Kaare Andrews
A bearded, decrepit Peter Parker works at a flower shop. A young couple complains that he sent cream roses instead of white, ruining their wedding. He understands and is willing to fix it but the couple leave, disgusted. Parker's boss, enraged that he has made yet another mistake, fires him for incompetence and halts his last paycheck to compensate for the wedding. This doesn't seem to bother Peter, as he simply walks out, depressed, carrying a bunch of white lilies.
As he walks the streets, Parker runs into one of the fleeing kids from the beginning scene, ruining his flowers and giving time for the officers of 'The Reign' to show up. Parker tries to reason with them, but not being as strong as he once was, is beaten up as he tries to pull them away. As the cops take the kid, the one remaining child despairs that Peter was too weak to stop them, and that no one can protect them now. Parker goes back to his apartment. While eating his dinner, he retains memories of his wife Mary-Jane, for who he had tried to get the flowers, and imagines her at the other end of his dining table.
Meanwhile, the mayor of New York, Mayor Waters, is interviewed by Daily Bugle reporters. He tells them that he's working on a laser barrier called the WEBB system to help protect New York from terrorist attacks - at the cost of having to remove metal ornamentation from buildings, bells, statues, and old crosses, to avoid interference. A Bugle reporter comments that, with all the success he is achieving now, he might one day spread his methods to the rest of the USA. However, once alone, the mayor is revealed to be keeping a prisoner an old, once-obese man, seemingly in a vegetative state, who lives off an IV drip -most probably Wilson Fisk, The "Kingpin"-. The mayor taunts him, proclaiming that he has always come and will always come every year to mock him for his bloated victory.
Back at Peter's apartment, a grumpy old man approaches the building, muttering about how terrible the world has become - it is none other than J. Jonah Jameson, who has come to visit his old friend. At the doorway, he tries to talk about 'old times' and wants to deliver a package, but Parker is too depressed to talk and simply slams the door in his face. Jameson pleads, telling Peter that he was sorry for unknowingly hating him all those years in the past, and that he sold the Bugle, feeling that he had run it on lies.
Getting no response, Jameson leaves, and begins to cause a stir, shouting about how the world is now full of liars and oppressors. Upon his bashing on the windshield of a parked car, two 'Reign' officers try to restrain him, but he just hits one of them. While the officers begin to beat up Jameson, Parker opens the package to find one of his old cameras from his days at the Daily Bugle, as well as a mask.
Jameson, cursing, calls for help as the Reign officers beat him. He screams that the city needs Parker, that he's got to do something and he's got to fight. He begins to apologize, and the officers ask whether the apology was for the car or the illegal brass knuckles he kept in his pocket. It turns out to be neither; Jameson was apologizing to Peter, who has donned a black mask and gone out in nothing but his underwear and socks. Jameson succeeded: Spider-Man has returned.
Spider-Man beats the Reign officers in his classic style while spouting abusive wisecracks. In his rage, he imagines himself to be young and musclebound once again, and flashes back to him catching his uncle's murderer, and subsequently brutally killing him by throwing him off a rooftop and crashing into the ground. The issue ends with Jameson asking if Spider-Man will return, saying this the city needs him. Parker punches him in the face, then wordlessly walks away.
The Sinister Six includes members Electro, Mysterio, Kraven the Hunter, The Sandman, Scorpion and Hydro-Man. Jameson prints fliers pronouncing the return of Spider-Man, and Waters orders the materials destroyed. In hiding, Jameson has a youth hacker post Peter's apartment location on all electronic devices throughout the city. Meanwhile, Peter, still seeing images of the long dead Mary Jane, begs her to pack and leave with him, because anyone can find him if Jameson could. A crowd has now gathered outside Peter's apartment, against all the laws that have been laid down. As the Reign attempt to bully the people home, the Hypno Hustler returns to play one last dance tune. Unfortunately, the batteries of his cassette player give out on him, and as he berates himself for not placing fresh ones in, the Reign shoot him down.
Outside, Waters' officers shoot Peter's apartment with a missile as Peter yells at her to pack when he realizes "Mary Jane" is smiling. Peter hallucinates that he is blasted to the street, and begins crying for help for "Mary Jane", when a car that "Mary Jane" is driving hits him. Back to reality, Peter is violently ejected from his apartment by the explosion of the missile, and finds himself in his black costume. A cheerful, wisecracking Spider-Man swings down into the officers who are hassling Jameson. Taunting the officers as they fail to bring him down despite their superior numbers and his advanced age, Spider-Man tears into the Reign officers. Jameson has the hacker broadcast the images of Spider-Man's assault to invigorate the crowd. Suddenly, the hacker is murdered by Kraven after his location is found. The hacker staggers before his life gives out, catching Spider-Man's attention for a crucial second, and the Sinner Six rip him apart. Kraven, screaming about not collecting his trophy for all those years he and Spider-man fought, rips Spider-man's mask off. The crowd sees him, an old man, crippled, defeated, and they lose heart. The Sinner Six badly defeat Spider-Man, but before he can be killed, they are beaten away by a set of mechanical arms, belonging to none other than...Dr. Octopus. The Multi-Limbed terror carries him away to a graveyard and starts digging. Peter drags himself to the three tombstones Otto set him by, and touches the names on them...Mary Jane Watson-Parker, May Parker, and Ben Parker.
Spider-Man is seen crawling the wall of the Reign building, which the Sinner Six are guarding inside. He creeps by the window and is unseen by the villains waiting inside. Bells can be heard ringing throughout the entire sequence. Below in the street is a group of civilians, and a child ringing the massive church bell. The bell torments surrounding symbiotes, and angers a nearby Venom. Venom demands that the mayor silences the bell; Sandman is contacted on the radio and is told to take care of the civilians. Sandman is reluctant with that order and argues that it's only a group of children. He says that the bell is the only thing standing between the gathering people and the monsters. Waters commands Sandman to silence the bell, or risk the chance that Waters could see the act as "Unpatriotic" and be forced to detonate the bomb within him. Sandman orders the children to leave, saying that if they left now they could keep the bell, and have a hope of surviving. The child ringing the bell then rebuts Sandmans statement about hope. She yells that hope has three daughters: anger, courage and truth. And at that moment, the girl removes her mask and Sandman is taken back on how she has the same eyes as him. As he is having a realization, the young girl turns into concrete.
The Reign recognize her as a "super" and open fire on her just as Sandman realizes that he is looking into the eyes of his young daughter, one that he never knew. As the Reign fire at the girl, the Sandman goes into a fury and attacks all the Reign officers as he tries to protect his daughter. But the damage that she sustained caused her limbs to break off as she is now clinging to life, spread across on the ground in pieces. Sandman goes up to her and cradles her in his arms. Soon a swarm of symbiotes begin looming over the father and daughter.
Venom informs Waters that he can sense Spider-Man near them, which prompts Waters to radio the Sinner Six. Electro shocks the building which knocks Spider-Man off, but he quickly recovers and kicks through the window where Electro was positioned. Hydroman appears beside Electro, and Spider-Man comments on how that is the lamest team up in history. Spider-Man kills them both by tripping Electro, thus making him fall on Hydro-Man. Flames erupt and incinerate Electro, and cause Hydroman to be reduced to nothing but steam.
As Spider-Man is crawling on the ceiling, Scorpion comes up from the bottom of the floor, saying how the Reign gave him a new suit that enables him to do whatever he can dream, which prompts Spider-Man to ask him if it can fly, as he kicks Scorpion out of a window and to his death. Suddenly a mist fills the room and Spider-Man recognizes the smell. He turns to find Mary Jane laughing at him and saying she never loved him. He punches her, revealing who he knew it to be, Mysterio. As he begins to walk away, Kraven reveals himself. He informs Spider-Man that some African warriors use mushrooms before battle, so that they can see their fears, and thus have nothing to fear in the battlefield. Kraven inhales the fumes that Mysterio carries and Spider-Man does the same. They begin to run towards each other. Spider-Man sees the faces of his greatest fears, Aunt May, Ben Parker, Mary Jane, and Jonah, but he had been seeing them all day, and was prepared. As Spider-Man rushes to Kraven, he wonders what Kraven must see, and as the scene turns to Kraven's perspective, he sees a giant rhinoceros attacking him. The battle ends as Spider-Man wraps him up in 16 cartridges of web. As he does, Sandman is trying to get his daughter to reattach herself, but she dies in his arms without Sandman ever knowing her name.
Spider-Man walks into a dark room where Venom finally reveals himself. Venom informs Spider-Man that he was behind the entire WEBB and the destruction of the super heroes. He tells Spider-Man that for all of his preaching of his need to take responsibility for every little thing in the world, he rejected his one single most important responsibility: Him. Venom angrily berates him for taking him from his home world, to a foreign planet, and once he realized that all the symbiote wanted was a companion, he left the symbiote to die.
Coming to realize the validity of Venom's point, Peter is lost for words. He says that he never even thought about that, where Venom mockingly points out that there was no way that Peter "The-World-Revolves-Around-Me" Parker could ever have. Venom says that he did this to show Peter that he could do what Spider-Man never could, protect the City of New York, and adds that now it's time for them all to die. A symbiote hand smashes through the glass and grabs Jameson, as Venom smothers Spider-Man. While Peter is being constrained, he has a vision of Mary Jane telling him that he has powers for a reason, and with those powers comes the responsibility of how to use them. Spider-Man breaks free of Venom's grasp and jumps out the office's window and to the top of the tower, with hundreds of symbiotes following. He decides that he needs to take the fight to a place where it can be seen by everyone, because even though he is walking towards his death, it would give the people hope and courage, and they will fight as well. As Peter climbs to his fate, Mayor Waters runs through the building and is confronted by a menacing Sandman.
On top of the building, Spider-Man prepares for his final battle, and the symbiotes charge him, ripping at him, tearing him apart. Peter knows that he can't survive much longer, and openly welcomes death. But right before the symbiotes can lay their final blow, Sandman comes to his aid, telling Spider-Man that all six of the Sinner's had bombs in them. Sandman then gives Peter the detonator and is devoured by the symbiotes. Peter knows what he must do. All the symbiotes leap at him as he clicks the detonator. The building then explodes.
Some time later, Jonah is shown on TV proclaiming that fear, crime, rape and super terrorists are back, and he couldn't be happier. The WEBB is no more. Crime is back to the city and masked heroes return. Peter stands wearing a hat and a trench coat, looking at Mary Jane's grave. He says that soon he will be with her, but not yet: he still has his responsibility.