We do this rather often. We fly into TPA to visit friends and then end our vacation at WDW, flying out of MCO. It's easy to do. As a previous poster noted, make sure you set your reservation up correctly (not returning to the same place). Also, if you think of it, ask for an Orlando map when you get your car at TPA. They don't always have one (at least at National), but they are very handy when you head for your new location. There is no "surcharge" for this. Sometimes it's even a cheaper rental to drop off somewhere other than your pickup point. (Of course, the reverse could be true, though I've not seen that.)