Favorite protagonist is probably Raziel from Legacy of Kain: Soul Reaver. Cast into the abyss by his creator, not for any fault of his own but simply because he was evolved, and made to endure a thousand years of agony, he still keeps it together very well. He's calm in the face of some pretty f'ed up shit, even going so far as to crack wise at some unknowable terror from beyond imagining which fancies itself a god. What tips him over the edge though was the utterly astounding job which was done with the voice acting. His is one of the few performances in which the spoken dialog actually feels right. It's a bit hokey, but I never felt the need to skip over it or be embarrassed by a bad performance.
Antagonist is a bit tougher, because there are a lot of good ones. I'll give it to Prince Luca Blight from Suikoden II, though. He's a pretty cookie-cutter bad guy, but he just takes it so damn far. He's evil in the truest sense. He has no far-reaching goals or great ambitions, he just wants to wreck people's shit. He doesn't just murder people, he makes them beg and degrade themselves to save their lives, then kills them anyway. He's also a hardass. In a game that gives you a party of six characters to work with, it takes three full parties to finally take the guy down AFTER his own army sells him out to you.