Don't try to power through it in two long days hoping they'll sleep most of the way - that's a recipe for misery. Break it into 5-6 hour driving chunks max, stop every couple hours for legs-stretching and bathroom breaks, and plan your overnight stays near stuff they'd actually want to do (not just whatever's cheapest).
For the actual route, I-75 straight down is pretty straightforward and has tons of rest stops, though it gets boring fast for kids. Mix in some detours - like the Georgia Aquarium in Atlanta or natural springs in Florida - and let them know about these stops ahead of time so they have something to look forward to. Pack a rotation of new small toys, books, or tablet games they haven't seen before, and honestly snacks are your friend even if it means more bathroom stops. Staying at places with pools helps burn off energy, and letting them pick one meal stop per day gives them some control over the trip.