Cir-El helps Superman fight off a diseased Bizarro. Later, she fights off with the aid of Natasha Irons and Girl 13, a vengeance-crazed superhuman ninja who is killing Superman. When Superman and Batman are said to be "captured" by President Lex Luthor in Superman/Batman "Public Enemies", Cir-El teams up with Superboy, Krypto, Natasha Irons, and the Batman Family to rescue them. Batman, not actually having been captured, is the one to save Cir-El and Superboy from a White House death trap.
Superman has a shock when, while talking to Cir-El, she changes into an angry young woman named Mia, who hates her Cir-El persona. Superman's Kryptonian robot Kelex subsequently confirms that Cir-El is not the Man of Steel's biological daughter (despite the evidence from S.T.A.R. Labs). While the girl's D.N.A. has some Kryptonian attributes, she is primarily human.
Disaster strikes when a future Superman appears and shows Superman a devastating future with Lois dying, Wonder Woman and Batman turned into cyborgs by a nano-tech virus concealed in "Yes" coffee, and Cir-El trapped in a giant Brainiac robot. Brainiac reveals that Cir-El is his "Trojan Horse", that he has concealed part of himself in the one thing he knows Superman would never harm: his 'child'. Cir-El was created by Brainiac by grafting some Kryptonian DNA onto the body of Mia. He then implanted false memories in Cir-El and had his servants, the Futuresmiths, send her out into the world (along with the nano-virus, which was placed in "Yes" coffee to proliferate the virus and infect the population) in order to unknowingly alter the future, and lead Superman to create a synthetic body to save Lois from her "Yes" infection in the future (for Brainiac to inhabit). Horrified, Cir-El throws herself into a time portal to prevent herself from being born, and thus, prevent the future from ever happening.
Thanks to the time-traveling efforts of Bizarro in Superman/Batman #24, Cir-El is able to join Linda Danvers, Kara Zor-El (both Modern Age and Pre-Crisis versions) and Power Girl to rescue Superman from the Source Wall. The girls are successful, but Superman only recognizes Kara, Power Girl, and Linda, due to Cir-El and pre-Crisis Kara Zor-El coming from previously erased timelines.
Cir-El and the other Supergirls then assist Superman and Batman in a reality-altering fight against various menaces from many alternate dimensions. At the conclusion of the fight, Mister Mxyzptlk sent Cir-El and everyone else involved back to their appropiate locations.
The only other human/Kryptonian hybrid, Superboy, inherited more traditional powers because his D.N.A. is 50 percent Kryptonian, whereas Cir-El's D.N.A. is primarily human, with some grafted-on Kryptonian attributes.