Diane:
I travel between WDW and Ft Myers all the time (I have a couple of timeshares on Sanibel island). I used to take US27, SR 29, SR80, I75. Taking that route, it was fine from about Sebring south. But in the last few years, US27 from I4 to Sebring has been getting worse and worse, with a lot of truck traffic. Last time I took I4, I75. It's longer distance wise, but took about the same amount of time. And traffic wasn't bad, so it didn't seem as frustrating. It takes me longer than 3 hours though. But that's probably because it can take an hour just to get from Sanibel over to I75. Another route that I haven't taken but other people have is US17 over to I75.
To the OP: I love that area, and if I ever moved to Florida, that's probably where I would end up.