Hi N.
I just did this trip with a 4mos, 32 mos, 34 mos and 4 y.o with another mom in our minivan.
We left early to miss city traffic. We learned that if we wanted the kids to fall right back to sleep, we had to make sure it was still dark out. That meant leaving by 4AM for the trip down. On the return trip, we decided to eat bkfst before hitting the road. Although the kids did not go back to sleep, it was actually a better trip. (And we saved money by using the hotel hot breakfast instead of having to buy something on the road.)
The halfway point is Chatanooga, TN. We found that the Holiday Inn Express consistently met our hotel criteria: safe area, good price, pool, interior corridor, clean comfy rooms. (We stayed one night at the one on I75). I would recommend booking a hotel room or multiple rooms around the area you plan to stop. We wasted so much time ensuring that we had a room, good rate and safe place. Most hotel policies have a 4PM cx policy. So you could make a decision while you were on your trip and just cx the extra rooms. Also, the room rates via internet tended to be better than when in person. Remember rates from Sun-Thu tend to be less expensive.
Although we probably could have made the trip straight through, we would have had to stop to feed the infant and we were less comfortable with stopping between GA and FL in the wee hours of the morning. Also, the kids loved the hotel experience as much as other parts of the trip. We would have dinner and always had swimming pool time.
We played car games like "I spy" and made up stories and pretended to do magic tricks. When we stopped at rest stops, we got the older kids out and encourage them to stretch and run. Every chance we had, we took the baby out. (I also brought the baby bumbo along and this was helpful.)
In the minivan there are side rest bins next to the carseats. I filled these with toys: little map, play cellphones and play cameras. We would play pretend games with these. THere was also a doodle pad. There were also some books and sticker/magic marker books. The sticker/magic marker books were a huge success. You fill the brush up wiht water and it colors in the paper. No mess.
We also had a portable dvd player. We would tell the kids that "after the next stop"or "after nap" we would play a dvd. It worked out well.
Good luck!