Assuming that you will indeed have 4 drivers, I would say that once it gets dark, you should rotate them every 2 hours at least. Plan for the youngest drivers to take the wee hours; older folks tend to have trouble with eyestrain when driving at night.
The older you get, generally, long-haul driving tends to become more difficult, especially if you are not used to being up really late. When I was single in my 20's and would drive through the night alone, it wasnt' nearly as difficult to stay awake and alert as it now, at 41, with sleeping passengers in the car. An interstate highway through the hinterlands is a very dull thing. With sleeping passengers, you can't crank up the sound system, or open up all the windows, or turn the AC on full blast. It can get REALLY difficult to stay awake in the wee hours when everyone around you is peacefully snoozing.
An aside for our UK friend: Yep, most Americans routinely will drive several hundred miles at a stretch. Six or seven hours at a time without more than a token stop is pretty common, the moreso the further west you live. Several times a month, my husband drives 5 hrs. each way for a business appt. that will last less than 2 hrs.; he leaves the house at 5 am and is home for a late dinner the same day (no trains or planes on the route, the only way to get from here to there is to drive.) I have a lot of family in the UK, and they are always amazed at how far we are willing to go in a day. I once decided to go visit my uncle in Newcastle for the afternoon; from London. I took the train, but everyone still thought I was insane to travel 3.5 hrs. each way for the sake of an afternoon's visit. Another English cousin of mine wanted to visit my sister in Louisiana during an Orlando trip; he backed out when he found out that he would have to fly 2 hrs from Orlando, then drive another 3 hrs. from New Orleans to her home.
