I agree, it's always best to get acquainted with the vanilla game first.
I'm not an avid mod user, but if you think you understand what's going on, Masterwork is probably a good place to start. From what I've gathered, it's a collection of a lot of miscellaneous mods and you can turn parts of it on and off; which sounds useful if you want to get an overview without downloading them individually. Also they don't deviate a lot from the vanilla fantasy setting.
If you like to take the game in an entirely different direction, though, that's possible, too. So, if you want to play in the post-apocalypse, or hunt for pokémon, you can.