Here's what I usually do with my guests on a three day trip to Cayo:
Leave San Pedro on the Tropic Air flight to Belize City Municipal (way cheaper than going to International). The wonderful people from Crystal Car Rental will pick us up at the airstrip, and we'll have a 4x4 Chevy or the new and more spacious Suzuki LX7 at a very reasonable rate.
From Belize City we go on the Western Highway to The Belize Zoo (a great little place without horrible small cages). Then directly to Caesar's Place at approx. mile 63 where we always have a fabulous meal, quite a few drinks and a good night's sleep.
Up early to go through San Ignacio (approx 11 miles) to the Mayan ruins of Xunantunich (about another 8 miles or so). Morning is best if you'd like to have the place to yourselves. After Xunantunich we do a quick tour of Benque Viejo and then stop at Clarissa Falls (about half way on the road back to San Ignacio) for an early lunch (more than fabulous Belizean Black Soup - it is a "must"). We then check in at the very, very nice San Ignacio Resort Hotel and spend the afternoon on an interesting trip (bad roads) to the 1,600 ft. waterfall and the Rio On Pools in the Mountain Pine Ridge area south of San Ignacio. You will be tired and full of fantastic experiences when you return, but not too tired to enjoy a great (and cheap) meal at your hotel. Still not tired? Then visit one of the many bars in the (almost) picture perfect Central American small town of San Ignacio (center is a five minutes walk from the hotel).
We leave early to go back on the Western Highway and turn south by Belmopan for a cruise down the beautiful Hummingbird Highway. We make a short stop by the Blue Hole (underground river coming up to the surface and a great swim), and then go back north and re-enter the Western Highway to Belize City. If there is time, a stop at Jaguar's Paw is important. You can do the zipline over the rainforest canopy or do cave tubing.
Then back to Belize City, where the guys from Crystal Cars will take you back to the airstrip for the late afternoon flight back to San Pedro.
Did this tour (again) last week and had a great time.
Well, just my way of doing it. Hope you can use some of the info for your first (and surely not last) visit to our beautiful country.
And... when you come back to the island you can stop by my beach bar and tell me all about it