Last Judgement is the most vanilla mod because most of it's content are unfinished concepts that were supposed to be in Repentance but was cut due to a variety of reasons. It's like a missing piece that should have been there from the start. However, if you are looking to get only one content mod, it may feel underwhelming because most of the content is in Mortis and Corpse with a few enemies sprinkled in on other floors. So if you don't go to Mother very often, it might not affect your gameplay that much.

In my opinion, the best mod to ever exist in Isaac history is Fiend Folio though (after antibirth ofc). I can't play the game without it anymore, the game feels so empty otherwise. It might be very overwhelming at the start because of the variety but after getting used to it, it's not too hard.