For years we sailed the keys in our C22. My wife taught in a year round school district and had 3 weeks off every 9 weeks so we spent many of them in the keys. Part of the time we trailered from the midwest and part of the time we found a place to store the boat in the keys. The biggest problem we had was finding adequate launch ramps. Our trailer had a tongue extension and we found many of the ramps too short to launch and especially retrieve the boat. The tides were very important because we needed every inch of water.
Other than that we had a great time. Find a copy of Frank Pappy's guide to the keys. We went to his lecture at the Atlantic City Sail Expo years ago and were sold on the keys.
I should add that after weeks of living on the C22 we found a rental condo with a slip that made our trips much more comfortable.
You might also consider a little further north. Charlotte Harbor, Sanibel, Ft Myers Pine Island, Cayo Costa.