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?
Silco from Arcane.
I often struggle with media villains, finding them unrealistic or unconvincing, but Silco is just so well-rounded and well-written, he elevates the quality of every other character he interacts with. In a series full of near- and actually-superpowered people, this weak, middle-aged man is the most terrifying and influential of them all.
spoiler
His absence from season two is one of the reasons why it flops compared to season one; Ambessa and Viktor are good characters, but weak villains.