Whether it's a stomach that's grumbling or a body that's chilly, being prepared for anything will keep your travelers happy and your trip enjoyable.
Bring food and water for everybody. Pack plenty of snacks for your trip--but be careful about what you bring. Nothing that drips or crumbles or stains. Good snacks might be bite-sized pretzels, cut up vegetables or small pieces of cheese. Water is the best drink to bring; it's healthy and won't cause big problems if it spills.
Save the fancy clothes for Grandma's house. No nice clothes are going to look nice after hours in the car. Dress the kids comfortably in layers... and bring along an extra sweater or sweatshirt in case it gets cold.
Take breaks! The whole idea of a road trip is to enjoy the trip... not just to get somewhere. Don't plan such an ambitious trip that you can't afford frequent breaks--you may see an attraction that wasn't listed in your guide book or you may just think a turn left looks more interesting than the turn right you were planning. Leave yourself plenty of extra time for new discoveries and bathroom breaks! And just stop the car to get out once in a while--throwing a frisbee or doing some jumping jacks will keep kids from getting restless and fidgety.