Trail of Cthulhu.
- Implied or explicit H.P. Lovecraft-inspired setting? Yes.
- Explicit mechanics for sanity, madness, dark insight, magic, and all the baggage that comes with a Lovecraftian setting? Yes.
- Potential to support combat that is interesting from a gamist perspective (ala D&D 4th ed)? Not quite so much. Combat isn't a primary interaction mode. It's relatively complex, but the general combat rules are 8 pages and it basically boils down to opposed skill rolls whose outcomes are modified by items and environmental factors.