I think that horrific fantasy is a great as a source for untapped potential.
Think about it, horror movies have recently started to come back into vogue. And even more recently in the spotlight is fantasy films. The two would mix great together.
I think a Call of Cthulhu film, if done right, could be an utter blockbuster. It should be one of those things that advances slowly and takes you by surprise, never overtly revealing whats happening, and not being totally understandable until the "twist" at the end, which would then make you wonder how you missed it, all the while scaring you silly with what you think is there, regardless of what actually is there.
It definately should not give you any hint going in that it has anything supernatural in it at all. No obvious titles that make it clear there is a fantasy element, and no trailers making it clear that the psycho cultist actually did make contact with something.
M. Night Shyamalan would be perfect to direct such a film.