Here are some of the things I did when my kids were younger:
DVD player with a few favorite movies along with a few new ones
CD/MP3 player with new music
Hand-held video games
Headphones...and a spare set or two
Small drawstring back pack with activities such as: coloring book/pages, colored pencils, pencil sharpener (had a bad experience with crayons melting in a car on an 85 degree day in PA. No crayons in our cars anymore); sticker and/or activity books; tablet for drawing; pipe cleaners or Bendaroos, magnetic play sets (like Colorforms but magnets), Colorforms; small figurines.
I always checked Dollar Tree, Five Below, the birthday favor sections at Target and Walmart, and the Dollar Spot (or whatever they call it now) at Target for fun little things to use in the car. If you have a AAA travel store near you, they usually have some fun little games for the car as well.
I always only put a few "activities" in the drawstring bag. I kept one extra activity hidden by my feet or under my seat and the rest were in a bin in the trunk/cargo space. If the kids got bored with the activities in the bag, I could get out the extra one at my feet. At the next stop, I'd get another one out of the trunk and hide it at my feet again. Some people will wrap each of these items like a gift just to add a little more fun to it. Be sure to keep a few things set aside for the drive home. I always had leftover things at the end of each trip because I'm a chronic over-packer.
We also took either small lap desks or used a rimmed cookie sheet and a travel pillow with a small sheet of rubber gripper shelf liner on top of it to keep the cookie sheet from sliding off. This provided a flat surface for coloring/drawing.
A cup holder or suction cup soap holder attached to the car window to hold colored pencils while using them.
A travel pillow and small blanket.
I also give each kid their own snack bag (again, you can just put a few things in it and refill from a secret stash as needed). It kept me from having to constantly hand out snacks (though I was traveling with 3-5 kids on any given trip). I always controlled the drinks and only handed them out as needed.
When the kids were young, we also made sure to take a frisbee, ball, and bubbles to use at rest stops to let the kids run off some pent-up energy.
I always keep a roll of quarters to use for "special treats" in the vending machines at the rest areas. While most machines take dollar bills, some of them are very fussy about the dollar bills they will accept so I try to save myself a headache and just use quarters. They also come in handy for vending machines at the hotel.
If the restaurant we stopped at for lunch had a play area for kids, I'd take the kids right to that area when we arrived. DH would go get food for me and him and we'd sit and let the kids play while we ate. When we were finished eating, we'd get their food to go and get back in the car to start traveling again. The kids would eat in the car and usually by the time they were finished eating, they'd be ready for a nap.
Pack a separate bag with clothing (including swimming suits) and toiletries you'll need for the overnight stay so you don't have to lug all of your bags in for the night. I made that mistake the first time we drove...and we were doing the drive over 3 days that time. After having to lug all of our stuff into the hotel room that first night, I spent a few minutes rearranging things and made sure we only needed to take 2 bags in the next night.
We keep this bag in an easy to reach spot in the car so we don't have to dig for it when we arrive at the hotel. I usually put an extra change of clothes for the kids in this bag in case we have any kind of spill in the car during the drive.
I make sure to have a small pack of baby wipes in the car for sticky hands and other mishaps during the drive. Also an old towel or two rolled up and stored under a seat can come in handy for many things. A roll of paper towels would work as well. I also keep a small Happy Meal size bucket lined with a ziploc bag in the car to use in case someone gets car sick (only happened once...now we know our son needs to eat something before we get in the car in the morning). Keep a few extra ziploc bags in the car...just in case.
You can also go to momsminivan.com to get some more ideas. We always do the license plate game. I print out a sheet for the drive down and the drive back. Our kids are older now (the youngest is 11) so they keep themselves occupied in the car for the most part, but DH & I still do the license plate game. We (including the kids), like to watch for and count all of the South of The Border signs. Unfortunately, there aren't nearly as many as there used to be. When we first started making this trip in 2001, we'd count ~100 signs. On our trip last year I don't think we even broke 50...but it's still something fun to do.