GLaDOS, or Genetic Lifeform and Disk Operating System, from Portal is one of the best antagonists in gaming in the past 5 years, easy. She is personified as evil, funny, and psychotic all while presenting more questions than answers, a trait all good antagonists should have. And she was popular enough to quickly become a meme after the public finally got it's hands on Valve's absolutely amazing puzzle game. I cannot wait for the sequel.
Oh, and the obsession with cake doesn't hurt at all.