US 301 from Dade City to Callahan works fine. If you want to go to Waycross take US 1 from Callahan.
I'd just stay on US 301 to Ludowici (notorious speed trap) then take US 25 all the way to Hendersonville. I have no idea mountain-road conditions above Greenville so that's debatable.
For the southern leg I'd do SR 29 from Immokalee to US 27 south of Palmdale, then US 27 to Clermont. Then from Clermont SR 50 west to CR 471 and north to Sumterville, joining US 301 there. If Clermont isn't interesting (lots of traffic) , take CR 474 south of Clermont to SR 33 north of Groveland, joining SR 50 there. They're good roads.
Bear in mind this entire route is rather slow complete with little towns, traffic lights etc., nothing like Interstates. I definitely wouldn't want to do that whole slog in two days.
