Holy crap, a game taking place in Orlando would probably be the best game ever.
It'd take place in and around our seven theme parks, with the tourists being the main thing at stake. There's tourists from just about everywhere in the city at any given moment, so everyone has some sort of tie to the story. Of course, it'd star me as the main good guy/badass, and everyone I know as supporting characters. There'd be levels set in Fantasyland, having a Peter Pan- themed rail shooter segment, another inside Space Mountain, a battle up to the top of the lighthouse at the entrance to Universal's Islands of Adventure, another among the inner workings of one of the dark rides at Disney, and an underwater level taking place in SeaWorld. Also, there'd be a few missions along International Drive (Wikipedia it). We'd also have an excuse not to have a sewer level, since it'd have to take place inside the Florida Aquifer, and that'd just be terrible.
Yup, best game ever. And that advergame Universal made way back when for the Gamecube doesn't count.
Honestly, though, Miami always gets a visit whenever the protagonists in any game, movie, or book go to Florida, and not Orlando. I've never been able to see why, though.