Lois Kills Stewie
Family Guy Season 6 Episode 5 (11/11/07)
After Lois identifies Stewie as her murderer, he takes the family hostage and blackmails the CIA into making him President of the World. Lois goes to stop Stewie by killing him. After an elaborate gun battle, Lois is unable to kill Stewie and just as he goes to kill her, Peter wastes Stewie. In the end, it's revealed it was all a simulation being run by Stewie to see what happened if he tried to kill Lois on the cruise.