Sometimes the issue is just the antagonist looking over at me and saying, "So what's my motivation?" I am by nature somebody whose natural tendency is to try to be accomodating and reasonable -- both of which are bad traits in a villain! So in my fantasy writing particularly I end up resorting to clichés of the "his dark god has driven him mad and he wants to obliterate the world" variety because anything less than that and my inclination is to have all parties negotiate an amicable settlement.
So I try to think about what people really are willing to kill over: money, power, sex, "us vs. them" (or "our god of brother love instead of theirs") -- all basically non-starters to me, but apparently not to the great throng of humanity. The psychology of my heroes is usually pretty straightforward "live and let live, but the bastards keep attacking me" and that I can get behind ... it's the psychology of the bastards that gives me trouble. And until I can get a handle on that, plot will continue to be a problem.