Don't skip the pit stops.
Many people just want to reach their destination for the day, stopping only when necessary for gas or restroom breaks. That may be fine for adults, but it generally makes for unhappy, fidgety kids.
At a minimum, stop every two to three hours so everyone can get out and stretch. No matter how young or old you are, it feels great to stand up, walk around and breathe in some fresh air. It also helps to let your kids run around a bit, especially if they're younger. Not only will it burn off some energy they've been accumulating in their seats, but it might tire them out enough so they'll nap when you're back on the road.