Enlist your kids' aid as navigators. Although it's best that you already know what route you are going to take, kids will feel more involved and engaged if you give them maps (simple, easy-to-understand ones) of your route. They may enjoy trying to spot silly place names or other interesting features along your route.
Give each kid a camera to take pictures at each stop along the route (or out of the car windows, if they don't mind blurry snaps). You can use single-use cameras or look for rugged, kid-proof digital cameras such as the ones offered by a number of toy manufacturers.
Pack a bag full of comic books, coloring books, books on tape, and the types of small games where the pieces won't get lost: magnetic games or slider puzzles. Do not distribute these at the start of the trip, but keep them in reserve for when the going gets rough. The novelty factor may buy you a little peace.
Plan for some active rest breaks. When you make a bathroom stop, get out a Frisbee, hack sack or ball to toss around for a bit before you get back in the car. This will help everyone to stretch their legs and have a bit of fun at the same time.
Bring along some pillows and even light blankets so that tired or bored kids can nap away the miles. Propped up with pillows, they should be able to fall asleep sitting up without too much difficulty.
