Malak from KoTOR and Traya from KoTOR II are possibly the most satisfying for me. Not because I hated them (Well, okay, maybe I hated Malak) but because the story properly builds up to them and they're hard at work giving you perhaps the most incentive to take them down during the final segments of the game.
And they are rightfully the hardest fights in the game.
And you feel awesome when you beat them.
And then there's Ghirahim and his boss Evil McDarkBad from Skyward Sword (Shut up, I still don't like his actual name). Those two dole out the hardest fights in the game, and gutting them got pretty intense for me. Unfortunately, they overlooked the fact that my ego is bigger my sword and skills are better than theirs. It wound up a heavily taunting daunting contest.