These are just some thoughts I had, and are in no way good ideas. I just like writing what I think and see what other people think.
One thing that I think would be interesting (albeit perhaps a bit expensive), is if you had different antagonists depending on the choices you make. I realize this isn't new at all, but I feel it's a bit more realistic. If someone plays as an unrelenting murderer of men and otherwise, while someone else plays a diplomat and "nice guy/gal", why should they be forced to fight against the same antagonist(s)? Hopefully though, the game will be much more complex than what i've just described, but several antagonist would be nice.
Also, seeing as they have heavily hinted this will be a franchise, i'd like to meet several antagonists that we never really end, or who outsmarts us perhaps in the later installments. How cool wouldn't it be if some antagonists were able to beat you, and the next time you would be meet them would be a game, or even several games later?
But to the real question in this topic, what make a villain you love to hate? If I hate a villain, I generally see that as a mediocre antagonist at best. I like antagonists that I, either hate to love (in which case I don't really hate them, I truly like them), or that I can understand and even condone. Antagonists which make me question myself and my "morals"
But yeah, while i'd like there to be a main antagonist(s), I feel that if there are a number of several memorable ones, that would make a far greater game than one with just one main antagonist. Also, i'd like to say that everyone in this topic has some great ideas, and hopefully Obsidian takes to heart the things we have to say. (My favourite so far would be, and I apologize if I am mistaken, but I believe it was agewisdom who brought the idea of an active, not passive antagonist(s); I really like that idea!