Choosing toys carefully can be most important. Something solid to lean on such as a clipboard can make coloring or puzzle books easier to use. Colorforms can be stuck on windows if every child has a window to decorate. Magnetic and electronic games are fun. Tiny dolls, plastic people and animals all work well. Pipe cleaners, aluminum foil, yarn, glue sticks, safety scissors and the like are terrific for creative kids. I find that letting each child take a lunchbox filled with these kinds of things passes the time very peacefully.
Rest areas on most major roadways occur about an hour apart. I've learned that it makes sense to stop about once an hour with children under ten years old. They can keep watch for the "Rest Area" signs, which can help keep them awake. Even non-readers can often recognize the distinctive signs and are usually very proud to be "reading."
At each rest area, we lock the car carefully. We then play tag or a similar game, on the grass if possible. Ten minutes of moving around makes everyone feel better. Then a quick snack and drink from our supplies, possibly laid out picnic style. This is followed by a trip to use the rest rooms, making sure to wash both hands and faces. We even carry toothbrushes and toothpaste and use them every second or third stop. It just keeps us feeling better and makes us less road-weary. Then everyone is ready to hit the road again.
These rest stops add about one hour to every four hours of driving, but the difference is that no one arrives feeling cranky and worn out. It also eliminates the stress and fighting that often occurs when kids are cooped up too long. Remember, you'll have to make some restroom stops anyway, and it's much easier to plan them than to suddenly hear, "I need to go to the bathroom", about thirty seconds after you've passed the exit. Or worse yet, having to stop and dig out clean pants because, "I didn't know I had to go!"