We now have three boys. With our oldest, we started with the box of art supplies (crayons, colored pencils, colored pipe cleaners, stickers, clay, etc.) That lasted a very long time for him, and he was great on flights! Our younger two boys are not so much into the projects, so we started looking for new ideas. I make a trip binder with information about the trip that they like to review and a "storybook" about the trip with pictures of things we will see/do for our pre-schooler. I've also done the surprise bags for particularly long flights - each of our boys gets on surprise bag each hour. (I bring along paper bags with their names on them, and put in a new surprise each hour - it's anything from a new movie to an activity book to food or gum.)
Now that our two older boys are pre-teens, they read, play DS or watch movies on their ipods. It's really tough for our pre-schooler because he's very active and doesn't do all the pipe cleaner animals, coloring books, etc. that our oldest used to enjoy. So he does watch some movies with the portable DVD player and we read to him. Otherwise, as previous poster mentioned, snacks are helpful!