I say go non-stop, because 2 hours in the airport + 4 hours of flying means that some part of the travel is likely to be during nap time. You really don't want to break up nap time in a strange situation where you don't have all your normal ways to comfort him. Trust me, but don't ask me how I know. I'm still hiding from all the people on that flight. :(
If he falls asleep in the car, try to time the flight to start just before his normal nap time. If he hates the car, try to time it so you're in the airport for naptime, or nap after you land.
You can book online if you're getting him his own seat. Remember that officially you cannot hold him during takeoff/landing if he has his own seat. Chances are that the flight attendant will be just fine if you need to hold him then, but there is the slim chance that you'll be told to put him in his seat and keep him there no matter what until the seat belt sign is off.
If he's a picky eater, take tons of food that he likes. If you bottle fed and he still uses a bottle, take more than you think you'll need.
Take lots of books or new toys.
If you babywear, you can keep him in his carrier through security (as long as there's no metal, so no ring slings). If you take your stroller, you'll have to fold it up and send it through the x-ray machine.
If you don't nurse or bottle feed, and he doesn't use a pacifier, um, ask your ped about ways to keep his ears equalized during take off and landing. He doesn't know how to yawn on command, and he can't chew gum. :) Otherwise, nurse/feed/give him his paci.