Chikara and LU have both had female champions and it was great. There was even a indie show mania weekend with a theme of all intergender matches. They're always well-booked, don't make the guy look like shit, and rarely come across as an unfair fight.

Me and my friends constantly fantasy book a build to Charlotte winning the WWE or Universal title. It'd make for a fantastic Mania moment, would provide great publicity, and would make a bigger statement than all the "firsts" they keep touting*. I don't think she'd look out-of-place at all against most of the top guys. Just don't book Brock and Braun to throw around ladies all willy nilly and you'll be fine. It'd open up a lot of possibilities, even for the smaller women who they'd never put up against the Romans of the world. Can you imagine a Sasha vs. Finn feud? Could be very entertaining.

*it'd piss off Saudi royalty though so they'll never do it