First of all you need to keep them busy or occupied.
I've traveled by car with my three kids since they were born and there's one thing we absolutely can't live without. It's a portable DVD player. They are pretty inexpensive. You can find one on sale for $40.
I select a couple movies that are gender neutral such as Finding Nemo, Shrek, The Incredibles, and Monsters Inc. When you let the kids chose you run the risk of arguing because the movie is too girly, etc. Boys don't usually enjoy watching princess movies and vice versa.
In addition to watching movies each kid has a binder that includes various printable games, activities, coloring pages and a stash of crayons, pencils, etc.
Here are a couple of the ones I really like.
License Plate Game Printable
ABC Game Printable and I Spy Bingo Game Printable Plus lots of helpful tips.
DIY Magnetic Board Games
Printable Hidden Picture Puzzles
Coloring Page Printables
For each kid create a box/bag full of serving-size snacks that they enjoy. Preferably non messy snacks they can eat by themselves. Some ideas include snack baggies full of gummies, trail mix, m&m's, goldfish, pretzels and raisins. If you have little ones let them pick out one snack every couple hours.
Kids get cranky when they are forced to sit for long periods of time. To avoid the crankiness - take lots of breaks so your kids can get out and stretch their legs. If you are driving, find a rest stop and let your kids run around after using the restroom. Bring along a beach ball, Frisbee, jump rope, etc.
Let you kids know where you plan to stop ahead of time. Consider giving them a map to follow your route as you go. This will help stop some of the "Are we there yet?" and "How much longer?" questions.
I remember when I was young my parents would leave our home in the evening, so my siblings and I would sleep most of the way. My parents would take turns sleeping and driving. It helps to bring a small blanket and travel pillow for each child if you hope for them to sleep during the trip.