I was toying with the idea of letting the PCs be native Barovians. My gut says that would work poorly, but it still seems interesting.
More likely, I'll prefer that replacement PCs come from some of the NPCs the party has run into. There could be some tweaks to class, to allow some customization, but it feels cleaner to have a player step into the role of Ireena, Ismark, or even Van Richten than for the group to trust a random passer-by in Ravenloft.
It could actually make for great horror roleplaying to have Ireena, as a PC, convinced that becoming Strahd's vampire bride will break the curse on Barovia and have to make that choice.