It's difficult to say a "must do" because it depends on the situation, I've done a lot of visits to Orlando and I don't think there is anything that I would say is a "must do" every trip, but there are a lot of favourites that get visited at least every other trip. To answer for someone else making a trip depends very much on their interests. But things I would say people on "one time trips" should at least consider ( outside the obvious main parks) would include.
Cirque du Soleil, DC, KSC, one Disney waterpark, a visit to Boma's ( great food and a chance to look round the fabulous AKL hotel) , for anyone heavy into art a visit to the Salvador Dali art museum in Tampa, BG Tampa (for coaster freaks), Bahama Breeze and to visit a few of the Disney hotels (preferably by eating in some of their restaurants).