We have traveled a lot - within less than a year, the we've been to 29 different states (including the Pacific Ocean, the Gulf Coast, and the Atlantic, in less than a month).
We like to travel.
Our three year old calls our vehicle, "home."
There are some good suggestions above. I would add/emphasize:
1. Stop frequently. If you're in AAA, get the books for the states you're going through. If not, plan out your route and then share it with friends/family and ask for suggestions for stops (long and short) along your route.
We usually stop every 2-3 hours, for 20 minutes to 2-3 hours depending on what we're stopping at (usually more like an hour or less). If you have a Garmin or other GPS type you can find parks to play in (nice stop!). If it's rainy, then we stop at Target or shopping malls and get out and move around in there, if there isn't a "point of interest" we want to stop at.
There are LOTS of free/low cost places to stop and visit - parks, zoos, etc. (St. Louis's zoo is free, for instance), too if cost is an issue. We have a National Park Pass and a membership in a museum which gets us in free at many other museums around the country. University campuses often have free museums/exhibits, too.
2. We have a travel case for crayons, and bring lots of coloring books and paper. We also bring lots of picture books (the Richard Scary books have lots of details to look at, for instance).
3. Toys - stuffed animals, small figurines which can be used for small level role playing. We have two small Doodle-pads that the girls use to draw on, too. We also have a small "Duplo" board and bring a box of duplos that they can build structures on while we're driving. We have a small travel case of Mr. Potato Head & Friends that they like to play with, too.
4. We bring a box of snacks for the road (pretzels etc.) and a cooler with drinks/fruit/veggies/string cheese etc.
Basically I just rotate through the toys etc. A typical day traveling for us would probably be:
Load up, choose toys.
Load up, choose different toys.
Meal (stop/stretch/run around).
Load up, choose toys.
Arrive at destination.
We do have a DVD player, but sometimes we go 3-4 days without watching anything; rainy dismal days, sometimes we go through two Pixar movies.
A GREAT game to play -- we call it the "horse game." Each kid gets a side of the road and you count horses on your side (parents help with this). Whoever has the most horses next time the vehicle stops, wins. And you start over again when you start driving again. If you're in a more urban area I suppose you could count churches or something like that, instead.