I can tell you one area that hasn't been overused yet. People are always looking at the antagonist to carry the horror, but really it's the setting that dictates much of the fear factor. For instance, make horror films based in a location where there is no simple escape, and make them claustrophobic. My favourite example of this is the game Penumbra, where you start off in a simple mine in frozen area of Greenland. As the mine goes deeper and deeper it turns into a bizarre facility as you learn the history of the place, being used by the military in WW II and eventually by scientists in later years. In this example, the main enemies are simply wolves, a giant death worm, and extraterrestrials, but each and every one is equally terrifying albeit simple.