My boys and I have done some long-ish road trips together. Given that we have 3 kids, still need car seats and boosters, and airports being what they are, we have found that driving when we can is a fun and economical way to travel, even including the cost and trouble of gas and hotels. We've come to look forward to our trips as special time together, as well as a way to get from point A to point B.
It helps to have a plan. Here's what has helped our family have a good time on the road.
Activities: Every kid has a pencil box of colored pencils and markers, sticky notes, tape, etc.. and a notebook of paper. If I need to push on when I don't think they'll want to, I keep a stash of crafts or toys to dispense as a bribe to get back in the car and keep going for a while, dollar toys, modeling wax (LOVE IT!), Wikki Stix, magic modeling clay (if you get white it's cheaper and then they can color it with their markers.), sticky notepads (great for making flip books), pipe cleaners, etc.. I tried beads once, that was a mess! Note: crayons will melt in a warm car, then leak through whatever they're in to find the lowest potential energy. Melted crayon does not come out of carpeting very well at all.
I also really like books on tape. I know a lot of families swear these days by portable DVD players and hand held gaming systems, but we haven't gone that route. What I really like about road trips is that we are all in one spot together sharing our experience for a good length of time. With DVD or electronic games, the driver isn't involved, and the kids don't interact with each other or the driver. With a book on tape we're all listening at the same time, sharing the experience. We stop it and talk about it, which is very fun. Also, because I have to turn it off when I need to concentrate, the kids tend to notice our surroundings and the traffic patterns more. They are actually helpful, being extra sets of eyes.
Food: We pack lots of healthy snacks and water, that way we don't eat junk and get grumpy and over-sugared because we were munchy when we stopped at the gas station. It also helps for any family where there are allergies or food issues. Rather than a gas station or fast food join, we tend to stop at the rest stops for snacks, picnic lunch, and running around when someone needs the toilet. We tend to feel like we really got a break when we play outside, which we don't get to do at commercial places. We'd rather eat McDonalds in the car and then have time to run and play when we find a park or rest stop.
Planning: Because I am the only adult, I'm doing all the driving myself. We stop at night, so I can sleep. I try to find hotels with swimming pools. I really like the AAA guides to help pick out places while on the road and then use the cellphone to call in a reservation - no hunting around a new town with a car full of fussy kids! (If you don't have a membership, you probably know someone who does and would be willing to lend you the books you'd need.) The novelty of swimming pools and cable TV makes the whole thing a great treat to the kids.
Stopping frequently is also helpful. On one leg of a journey my husband joined us, and so we didn't need to stop as often, or as soon. The kids really hated it! Taking a break every ~3 hrs and driving no more than 8hrs in a day really seem to work better for them. Driving at night while they slept might be an exception that would work.
In addition to designated rest stops, we have enjoyed visiting museums and sights along the way. With our membership to a local museum we get a list of reciprocal museums that we get into for free. We plan ahead to use as many of these for our rest/play stops as possible. We've had so much fun with this that the children now ask in advance what museums we'll be getting to see on our road trips.