Graham is right. It all depends on weather.
You have to launch from the beach and you have to take whatever gear you used to launch with you. You have to get under the bridge that Graham mentioned, which means that you have to strike masts and sails. You have to get through the shallows of Florida Bay. You have to navigate through shallows, wave-battered passes with contrary tides, and open water. You must have propulsion for when there is no wind.
The race has been won by a Laser, a Paradox mini-cruiser, a Texas Water Safari canoe (in terrible weather with below freezing temperatures in the 'Glades and winds over 40 knots at times), a schooner rigged canoe, a NorseBoat, and the Core Sound 17. If you look at the top five or so, you will see an amazing assortment, including multi-hulls. Salty Frog, Riverslayer and Shar Chow are always near the top in off-the-shelf kayaks and kit stitch-and-glue kayaks, and they would have a tremendous advantaage in really bad weather.
If there is little or no wind, XLXS with his Huki wave ski will only be handicapped by needing to rest, though my bet is always on a tandem boat that can keep going 24 hours.
It's a lot of fun. Watch and see.
Doug (aka Ridgerunner)