This is just me, but I'd leave a little earlier than that, and taking a good nap prior to leaving. We left with a 2 1/2 yr old, 6 month old, a 14 yr old baby-sitter (cousin of same last name) and the two of us. We left just after midnight on a Saturday night and I drove non-stop to Morgantown, PA. Stopped to fill up the tank, our bellies and church and, with a full belly, my wife drove an hour! I took over again and drove till 2:00PM into Charlotte, NC. Gave the kids a chance to run around (ok our 2 1/2 yr old and changed the newborn's diaper) and my wife drove us to Savannah, GA. We stopped for the night there and it was a short drive to Orlando, with a pitstop in Jacksonville for lunch. (I drove the whole time 2nd day). Yes I was tired afterwards, but we could relax easily after that.
We found that by doing it this way, the kids slept through a lot of the driving and we had a lot less crying in the back because they were getting restless. Just remember to allow the kids some running time at fuel stops. They should not be only to fill up and go, but allow for minimum 1/2 hour.
Without kids, we did Mississauga to Miami in 21.5 hours, non-stop but switching drivers every 3 hours or so.