We just drove to Florida over April vacation. 5 of us in a station wagon. (2 adults, one teenager, a toddler and a baby)  and it went well.  A few must haves:

• DVD Player. Especially for bigger kids. We barely used the one we had, but it came in very handy in moments of desperation and exhaustion. I would recommend it to anyone.
• For babies in car seats: Well worth it to invest in a travel tray. There is a website "Traveling with kids" which is very helpful. I have one if you want to rent it. It allowed my 22 month old to have some toys and books in fromt of him without losing them. He even colored.
• I also invested in little pillows to go around their head, designed for the car seat too. It supports their head, and neck well, and allows them to sleep for hours without head bobbing the whole time.
• Great idea to have plenty of little toys in a bag, to hand them whenever they get tired of whatever they're playing with. Babies don't have a large attention span. YOu don't have to spend a fortune. I went to the local dollar store, and found plenty of things, like plastic animals, cars, books, baby mirrors, baby toys, etc etc etc. Great place to go when you're looking for inexpensive distractions to save your trip.
• Plenty of snacks are a must too. Of course think of easy to clean and wipe, so they don't get all sticky, since stops should be kept to a minimum, to avoid temper tantrums when they want to stay out of the car and you want to keep going.
• Puppets, books, music to distract them are good. Sing along songs, music, little quiet instruments, etc.
• Depending on preference, we left at night, and drive throught the night, while they could sleep. It gave us about 6 hours of peaceful driving. Then we stopped to eat, stretch, run a little bit.
• Leave enough time for stops. Rushing when you stop won't help anyone, especially not the kids. They need to run, play, stretch, and have some fun.
• If you have a teenager, they have their own ways to entertain themselves. My son and his iPod were best friends during the entire vacation.
• The drive to Florida was 24 hours for us, so we planned to visit family in NC for a night or two to cut the trip in half. 12 hours of driving instead of 24. Then you can make it more enjoyable for everyone by splitting the day into meals, and play times, or night driving if that's the case.