We make the twelve-hour drive from Raleigh to Toledo (The Motherland) fairly regularly. At one point, when I was still a bratty teenager, we went eleven times in a single calendar year. One thing I've discovered is that you have to balance "alone" time with "together" time. If everybody's engrossed in their GBA/Discman/book/whatever the whole time, you arrive feeling disconnected and woozy. If you insist in playing "family car games" the whole time, you hate one another by the time you cross the second state line.
Books on tape/CD are great because they give you something to talk about but also don't require interaction. I suggest light, funny selections like "The Hitchiker's Guide to the Galaxy" or something else that doesn't require absolute concentration. Personally, I have a problem with being read to, and I can't absorb information as readily that way -- quite the opposite of Pedro in that respect -- so I've found that if the audio selection is too informative, I tend to learn nothing from it.
Car games:
The Alphabet Game: look for the various letters of the alphabet, in order, on roadside signs, including billboards. Can be played cooperatively (all players call out letters as they see them) or competitively (players keep track silently, and try to be the first to get to "z" -- not recommended if your spouse cheats at games).
I Spy: A perennial favorite.
Backseat Bingo -- not as dirty as it sounds.
Purchase or
make bingo cards with common roadside sights -- signs, other cars, even different kinds of roadkill -- and check off the objects as you see them. My family and I had the cards with the red sliders, and they were awesome. Unfortunately, the driver usually isn't able to play (safely) unless someone else manages her card.
A variation on Backseat Bingo is to see how many different states you can find represented on license plates. The first one to spot a new state gets a point, and the person with the most points at the end of the trip wins.
If all else fails, down some dramamine and pass out. Nothing makes time fly like a good afternoon's sleep.
Bon Voyage!