lots of variables here
We've crossed the lake on our H33 with a 4' draft, no problems as long as it has been raining. The lake has a tendency to get very thin in the dry months and the summer storms make crossing quite a challenging sail (the lake is bigger than many realize). That canal runs from Ft. Myers east to St. Lucie. As for the keys run, dont even try the beer can channel that cuts just under Flamingo to the upper keys (Key Largo) unless you are very familiar with those channels in upper Florida bay and/or have a boat with a shallow draft (less than 3' and easy to get off a sand bar). Probably our favorite way to cross is from Naples to Shark River in the Everglades for the night or two. The fishing in there is just amazing, 50lb. test might not come close to holding some of those critters that lurk in the Glades after sunset along the coast. From there we day-sail to marathon and set up shop in Boot Key Harbor. There you can re-provision, rest, drink, shower or whatever. West Marine has a dingy dock you can use to replace what you lost on the way down. At this point use the Gulf Stream to boomerang you to the western Bahamas with an overnight sail. The only two words of cautions are the crab pots in Florida bay, they are thick. If you overnight it down there watch carefully. They have wrapped many-a-shafts. We've wrapped so many times that we installed "Strippers" on our shaft, so far so good. The other warning is the Gulf Stream in winter, watch it, she gets ugly if the wind is from any northern direction.