That could work.
You know, right when I finished that post I thought to myself, "Okay self, how would you feel about Paulina Atreides as the protagonist??". I thought about it and I really don't think I'd have a problem with it. Except then I remembered that part of what makes Paul special is the fact that he's trained as a bene gesserit and that's a thing usually reserved only for women, so it might not work for Dune.
Baroness Harkonnen tho? Why not?