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?
The Prophet of Truth from Halo 2. Cunning bastard, one of 3 prophets at the helm of an immense alien civilization, manages to get the other two eliminated, apppropriating all the power, creating a martyr and exacerbating the passion against the human enemy in the process, observes that one caste (the Sangheili) is a little too smart to keep buying his lies so replaces them with a more brutish, loyal caste, the Jiralhanae…
Best voice actor of the game by far, too.
Such a clever weasel