As usual, it depends upon WHERE you're headed in Florida. For Tampa/St. Pete/Sarasota: I-81 to I-77 to Charlotte and I-85 South to Atlanta (don't get folks started on Atlanta!) to I-75. Even if you're headed to Orlando, the Florida Turnpike off I-75 is preferable to the I-95/I-4 route. If you're going to Miami/South Florida/The Keys: I-81 to I-77 to Columbia, SC, then I-26 to I-95. Once you get to Fort Pierce, you can bail onto the Turnpike and into Ft. Lauderdale, The Palm Beaches, Miami and the Keys. The Turnpike's kinda pricey, but if you can get a transponder for your rig at one of the service plazas, it'll save you some coin. I think it's still $25 for a t'ponder and you have to pony up another at least $25 for your initial account opener.