Hey Dave, if you are open to other possibilities I'd recommend you look into renting a condo or townhouse. I rent a townhouse in Key West and it's comparable in price to a hotel but it's so much better - private pool, kitchen, 3 BR 3 Bath, etc. There are a number of places that list residences for rent and personally I like them better than hotel rooms.
As far as guides, you will have a tough time getting a top guide for that time frame unless one gets a cancellation. All the established guides are pretty much booked from the beginning of May through June. If you are going to Key West I'd recommend looking up the Saltwater Angler - they have relationships with a number of guides and can hook you up with a less established guide.