Not necessarily. The only thing that really changes is how they'll react to the dangers lurking inside the mansion. For example, while a "newbie" like Ethan will be immediately overwhelmed and have getting the hell out of there as his top priority, a seasoned vet like Chris, Leon, Jill, etc. will be more confrontational with the available resources while still ultimately being on the lookout. In the end, their motivations are pretty much the same: survival.
Plus, who's to say that someone like Natalex isn't capable of bringing unique threats (or even becoming one herself) that the seasoned veterans haven't seen before? Her whole backstory is predicated on not only replicating, but
surpassing her brother's unreachable heights (she's literally trying to become immortal FFS and has a contingency plan in place like no other RE villain could possibly
dream to think up), and given what we already know about her methods and demeanor in
Revelations 2, she's certainly capable of pushing the vets to their limits in ways no one else before her ever has. Hence, it could, more or less play out the same way with the older characters if done correctly, it's called
writing. Yes, the older characters are otherworldly, but they're also dealing with otherworldly threats that are only growing impossibly stronger with each numbered installment (or, more accurately, with each new deus ex machinistic virus).
Hell, if anything, I'd say Natalex (or any Wesker) would be too OP for a new, "ordinary," "rookie"-type character. Again with characters meeting the circumstances.
Except, as somebody else pointed out earlier, the
RE5 leaked audio proves that Chris is, at most bisexual if not completely straight. Of course, that's not to say he doesn't also desire a little "meat" on the side, it's certainly possible (hey, more power to him), but we have mere subtle anecdotes (from male and female RE fans alike) as opposed to leaked audio from the game flat out confirming he's interested in women.
On a side note, Jill did sound a little... "jelly" LMAO.