Karen "Heavy Flo" Griffin
When Karen was 14, she came out as a lesbian, angering Francis into kicking her out of the house and practically disowning her. She grew to hate him for his intolerance and later on, she hated her mother, for supporting his decision.
Karen started up her own life, working as a wrestler, bulking up and making dough, until she had enough money to buy an apartment, get a job, and slowly crawl her way up in life. At the age of 24, she met the girl of her dreams, at a lesbian bar, Heather Sung. The two girls became girlfriends.
It wasn't until a while after Thelma's death in "Mom's the Word", that Karen felt comfortable with returning to her family again. After all, she still loved Peter and desperately wanted to see him again. As soon as her parents were out of the way, the window was open for her to go back to the family.
On Thanksgiving, Karen drops in for a surprise visit in "Peter's Sister", leaving the whole family surprised to learn that Peter even had a sister. Peter admits, he's never mentioned his sister, due to him being very ashamed by her. This is of course, due to the fact that Karen always beats him up and dominates him at everything.
Lois is rightfully inquisitive as to why Karen was absent during major Griffin family events, such as the funerals of her own parents and Karen explains the whole story.
Meg discovers that Karen treats Peter the same way that Peter treats herself. Although happy at first after her dad treated her like dirt all those years and was finally getting a taste of his own medicine, she realizes that Karen takes things too far and decides to work with Peter to even the odds. Peter challenges her to a female wrestling match where she is close to beating him, when Meg appears and whacks her with a chair, resulting in a serious injury and coma. While she is in the hospital, Peter rejects helping her by refusing to have his blood type checked.
In "Handling Karen", Karen comes by for another visit and introduces the family to her girlfriend, Heather.
In "Bride Whores", Karen and Heather get married.
In "Little Orphan Stewie", Karen and Heather consider adopting a baby but they don't know if they can handle one, so they take care of Stewie to see if they're any good at it. They end up being horrible at it but the lesson they learn is not that they shouldn't have a kid it's just that they shouldn't adopt and they decide to get a sperm donation. This sperm donation kid isn't seen until later in the show.
In "A House Full of Peters", Peter meets his many sperm donation kids for the first time. He takes notice of how one of the kids, Hubert seems to be extremely jacked up. It soon comes about that the woman who received his anonymous sperm donation was his sister, Karen, not knowing the donation came from her brother.