First off, nearly two pages worth of comments and we've left off some of the blatantly obvious. Instead, we're focusing almost entirely on JRPG characters . . . LAME
The most evil villian to appear in a video game is (well, I THOUGHT it was obvious)
DARTH VADER.
Followed closely by SAURON and HITLER.
We've also had COBRA COMMANDER, MEGATRON, and SKELETOR. DRACULA, FRANKENSTEIN, THE MUMMY, and THE WOLFMAN. MAGNETO, DOCTOR DOOM, and LEX LUTHOR. (EDIT: I could be wrong on one or two of those, but I'm almost 100% sure that each of them have appeared in a video game in SOME form or another.)
Heck, even THE UNDERTAKER ranks higher on the badass-o-meter than whiny, confused, just needs a mother-who-will-love-him-for-who-he-is Sepiroth.
Now, for those who want original video game IP (which was not part of the question), there are
1. Ganon (Dorf, if you prefer, whatever)
2. Bowser
3. Darth Revan (KOTOR)
4. Kryptosporidium (Destroy all Humans)
5. Kain (Legacy of)
