Well, since no-one's thrown in any thoughts yet, I'll chip a couple in to see if I can't help get shit rolling.
The Resident Evil games have always had themes of mystery and conspiracy about them; of things not being quite as they seem (even the first film managed to pick up on some of this, before the sequels went off and did their own thing). You've usually got themes of corporate evil going on as well, in the form of the Umbrella Corporation, though I've always enjoyed most the games that stray away from that and do their own thing (just take a look at 4 or even Revelations as good examples).
Have mysteries to solve, a conspiracy to unearth alongside bio-organic horrors; mutated monster things are cool, but they can't carry a plot all to themselves. If you have bizarre goings-on surrounding such gribbly monsters, however, you've got something to drive the story alongside scary shit. It's a good combination.