Vanilla. No mods, and no CC. It's easier to upkeep, and I'll know for sure that if any issues arrive in the game, it's either the game's fault or my PC and not some random bit of CC or a mod I'd have to chase down every single time.
Can't tell you how many times I'll see people post supposed 'bugs' with the game, going on and on about how the gurus need to fix this or that, only to come back later and say it was CC x or mod y. Or issues with the gallery or whatever. If I ask the gurus for a fix, I'd like to know for sure it's their mistake to fix first, lol.