In addition to all the old favorites such as "I Spy", finding the alphabet in order on billboards and signs, and making sentences from the letters on car tags, our family has a couple of other favorites.  Before your trip, go through magazines and catalogs, or sketch out pictures of things that you might spot as you travel.  Examples are campers, moving vans, dogs, stop signs, traffic lights, construction barrels, red cars or white trucks, trees, flowers, cows, horses, swimming pools, 18 wheelers, cell towers, bridges, rivers, golfers, fishermen.....Think through all the things you see when you are traveling on the interstate.  I usually fill up the front and back of a page with a combination of cut-outs and simple sketches for each child.  Then have your children keep a look-out for the things on their page, and circle the ones they find.  For younger children keep it at easy-to-spot things, like clouds, fences, flowers, etc.  I've even done, "Find the color green" or a blue sign.  For older children include harder to spot items. 

Another game that I just bought at a used book sale is "Jigquiz".  It is actually a card game, but I easily adapted it to a car game.  You could also easily make your own.  I held 2 stacks of cards-one with random letters, and one with the "question".   Examples of "questions" are: "a word ending with 'ent' ", "something you buy at the super market", "a river",  "a color",  "a book", "a word with 8 letters", "something you wear", etc.   Draw a letter card and announce what it is to everyone.  Then draw a question card and read it aloud.  The answer must start with the letter on your letter card.  Whoever calls out a right answer first gets the card.  Then on to the next letter and question.  We played this on a 45 min. trip last week, and the whole family joined in to play-teens and all.  Even the 5 year old got in on it (and won 2 cards!)  We had such fun, and the trip went by in no time.