There's a few that would make frankly interesting surprise champs, at least in terms of the WWE/World Heavyweight Championships. I read MVP mentioned, and I'd agree that would be a surprise when it comes to those two, although mid-card championships are no surprise at all. One that would be a surprise would be Evan Bourne, particularly with the run he's had lately. But then, smaller wrestler, with the exception of Rey Mysterio, they tend to reach no further than contendership. I blame Vince for that.
I'd make one exception, but not for any extended period, likely to lose any Heavyweight Championship on first title defense. That'd be Hornswoggle. Impossible, you say? Well, as we all know, getting a title has nothing to do with realism and everything to do with how big a draw for crowds and merchandise the wrestler is. I could definately see a special circumstance in which, through trickery and loophole exploitation, Horny manages to get the belt, but loses it the first time he's forced to wrestle "legitimately" (unless there's a disqualification and I can definitely see him exploiting that loophole a few times.)
Santino would be a great surprise as would Jamie Noble. Say what you like, but for his size, the guy's an incredible wrestler, just about revolutionized the cruserweight division (even by admission of several of the other WWE superstars) and he has a great comedic character. It's time for a comedic champ! I'd like to see this guy at least get the ECW Heavyweight Championship one of these days.