For what it's worth, I've done it as a PAX from Naples to Key West in a C152.
My advice is to fly down the Keys rather than straight across... apart from anything else, the Keys are beautiful to look at from the air.
Chap at Naples Air Centre advised us to take life presevers and lent us some sort of foam jobbies which don't inflate. We stopped at Tamiami to put them on but they were a bit uncomfortable so we didn't bother on the way back. We figured that with one PPL and one "competent at the controls" in the event of the donkey quitting we'd have time from 3000 to get the things on, but this is definitely NOT recommended advice! Get inflatables if you can.
We followed the road from Naples straight across to Tamiami and then down the Keys, but flew back up the Keys to Homestead Municiple and then direct to Everglades City, thence to Naples. You're right - if it goes quiet over the Everglades there aren't many places to put down safely, and the swamps are full of 'gators! Tip: don't land at Everglades City on a hot afternoon, the threshold is right on the water's edge and we experienced something very similar to winshear which led to a rather firm arrival! Went round and tried again with a shallower approach and power - flew out of it the second time and called it a day!
The water surrounding the Keys is very shallow; if you have to ditch you can do so close to solid land - if you go straight across what - if any - land there is mostly mangove swamp; why take the slight risk of several uncomfortable hours in the water worrying about sharks (and I think you'll find they are there) while the USCG are (hopefully) looking for you!
There is also Marathon Airport about two thirds of the way down if you fancy a stop and there are some private strips enroute as well if you need to make a precautionary.
You'll need to talk to Key West NAS on the way down, but they were helpful and gave us a good view of a couple of Hornets!
Be mindful of the Balloon Cable to 14,000 ft near Key West! Marked on the sectional of course...
NAC will certainly give you plenty of good advice and I don't think you need worry about it, follow the road both ways and you'll be OK! Hope this is of help!
Enjoy it! We did, and we had a cracking lunch in the town...