What's brilliant about Sephiroth and why he's just as much of a mascot of FFVII as Cloud is due to how he was introduced in the game. Instead of him being shown as the madman he became, you first see him when he was sane and then went through the entire Nibelheim incident in which he discovers his origins and then slaughters an entire town. I can't name another villain in a game where you see something like that. Most of the time with villains you see them after the fact where they're ruthless and cruel, and then the writers try to put in some bullshit sob story to make them "complex." It's interesting how a change of order can do so much to make a villain stand out.
Some others I'd put in:
King Valentine, Odin Sphere: The ruler of a great kingdom now reduced to a raving lunatic. The game also does a great job of using its multiple viewpoints to show different aspects of him.
Yuuki Terumi, Blazblue: Holy FUCK, this guy is a piece of shit. And I can't help but be entertained by him due to his endless trolling and scenery-swallowing delivery. Truly the King of Trolls
YHWH, Shin Megami Tensei: Probably the most brutal, evil, and petty depiction of the Almighty since Preacher. He's really a broken tyrant who craves worship and essentially throws tantrums when he can't get his way. Beating him in any of the titles is far too satisfying.
Albert Wesker, Resident Evil: Social Darwinist, treacherous, manipulative, and he wears sunglasses at night. Definitely a scumbag only out for himself who throws away those whose usefulness has run out.
Dracula, Castlevania: The King of the Night, the Sacred Ancestor, call him what you will, Dracula is one of the kings of being an evil overlord. His centuries-long battle with the Belmont Clan is one of gaming's classic rivalries.