A lot of my more mainstream favourites are already picked, like Sephiroth, who never fails to send a chill down my spine (partially due to Uematsu's amazing musical theme for him), so I'm going to go with a more obscure villain who legitimately filled me with loathing and dread whenever she was onscreen:
Kuroki Mio from "Pretty Guardian Sailor Moon" (The Sailor Moon Live Action Series). Basically she's a new classmate of Usagi's who turns up and proceeds to just be horribly manipulative, trying to turn the students against Usagi, humiliate and isolate her while maintaining a really sweet facade. She's a sort of teenage incarnation/clone of queen Beryl, and she's terrifying because usually the school stuff in Sailor Moon is so separated from the senshi stuff, and Usagi's problems as Sailor Moon are usually fixed by shooting sparkles at a monster, but Mio just can't be stopped like that. The main feature though is, the actress' performance. She has a disconcertingly huge grin and an uncanny ability to smile with just her mouth while her eyes look like she's plotting your murder.