It would add to the gameplay, maybe ghouls and mutants don't deal with rads, but have other problems then a human would have to deal with. have them have different pluses and minuses, so maybe this is good at this, but is very bad when it comes to this. maybe have it so ghouls don't get attacked by this (federal ghouls), but get attacked by that (brotherhood of steel); ghouls can't go here, but can go there, etc. etc. same with humans and super mutants. it would add more to the game, where you can't do this in one playthrough, but can in this playthrough. plus it would make sense to the story if they didn't start in a vault.
tell us what you think, and I really don't think it would screw the game up if you can still choose to be a human, but if you hate it, tell us why.