Sin and Zeromus are the only villains of a mainstream FF that were never defeated in a fair fight.

Chaos: Defeated by the Light Warriors, twice. Apart from being well-hidden, he wasn't much of a fighter.
Emporer Palamecia: Both his human and final form were crushed by Frioniel and friends.
Dark Cloud: I think he was in the same boat as Chaos.
Zeromus: Was invincible to anything and everything FuSoYa, Golbez and your party threw at him until Cecil used the Crystal. Even supposing a villain got his hands on the crystal, it would be useless because a man of darkness using it means nothing to Zeromus.
ExDeath: He was beaten by Galuf in a one-on-one fight just before Galuf died. He also lost the final fight of the game.
Kefka: Beaten by the Returners, at least twice.
Sephiroth: Omnislashed into oblivion.
Ultimecia: Again, killed by Squall and the others.
Kefka: Even though the mighty planet-busting Kuja was not killed by the main party, he did lose to Zidane and co., but he still won the war with his Ultima.
Sin: All front-on attacks were useless against him. Operation Mi'ihen was a slaughter, and the Final Summoning only provided temporary defeat (not that a villain could use it anyway). The Hymn of the Fayth eventually made him docile enough to be breached and taken down from inside (though Overdrive Sin still had the most devastating technique ever seen in a Final Fantasy game, Giga Gravitron). Now, I don't think any villain would know the Hymn of the Fayth, so there's no way they could get close enough without being crushed like an ant by GG.
Vayne: Never finished XII, but I read he was defeated as the Undying.

Since there's nothing to suggest he could be taken down by any of those guys, we can assume, if the fight went on long enough, he would kill everyone except Zeromus.