For me, it would be GLaDOS.
Portal 2 spoiler
She deleted the one remaining human part of herself because it was just too much to deal with. She releases you at the end of Portal 2 as a path of least resistance measure because “killing you is hard.”
What about you, what is your favorite media villain?
Scorpius from Farscape is a fantastic villain. He was meant to be a one off villain of the week for a clip show. By the time the episode was finished it was a two parter that had only a few seconds of clips, and instead set up the plot elements that would drive the rest of the series, with Scorpius at the heart of it all.
He’s one of the rare genius villains that’s actually written well enough to seem smart. He’s ruthless but not unreasonable. He’s horrific, but also charming. He’s a bottomless pit of hatred and vengeance, and yet he is cold and calculating, perpetually in control. I’ve heard him described as mirror universe spock turned up to 11 and I kind of agree.
Plus, we also get Harvey.
See also: David Xanatos. Imagine if Bruce Wayne put all that effort and planning into villainy, mad science and sorcery, theoretically for money but really just for the fun of it. Now give him an Iron Man suit and the voice of Jonathan Frakes. He’s an evil genius that’s so good at what he does that his name is literally synonymous with plans can only end in a win.
There’s a facet of Xanatos that puts him into the top tier of villains: he never seeks revenge. At some point nearly every character in Gargoyles goes out looking to get revenge on someone who wronged them, but Xanatos just keeps on trying to make himself powerful and immortal and not letting himself get wrapped around the axle trying to destroy the main characters. Shredder, Lex Luthor, Voldemort, Joker… so many villains are defined by their obsessive fixation on their heroes. Not Xanatos, because he’s too fucking cool to be bothered.