Have you considered a dose of Benedryl??!
Haven't had to resort to that yet for our 2 1/2 year old--but I keep it in the back of my mind.
We have been traveling with our daughter since she was 11 weeks old. A few tips to keep you (and the other passengers who are a captive audience to your kid's every whine) happy:
1. If you have a very active and easily irritated child like my daughter, spend a few bucks more and pick a flight time that best suits their schedule. Each child is different, so it may mean traveling at their "best time" of the day--or perhaps at nap time. For example, out of Detroit, those real early morning flights are always the cheapest--but for us, it's not worth having a cranky child all day.
2. We also always spring for the non-stops--worth every penny.
3. We always buy her her own seat and take her car seat on board. Since she has accepted that she can't get out of it in a car; she has accepted she can't get out of it on a plane either. She is also familiar and comfortable with it. We don't let her out of that car seat unless she really has to be changed or the plane is on fire. Once she is out of the car seat--the game's over. (Plus, if you are renting a car, you will need a carseat anyway.)
4. I take a bottomless tote bag full of all sorts of things to do--new books, other new small toys, a magna doodle, lots of snacks, etc. For example, my daughter loves fruit snacks. I personally don't care if she eats 10 packs of fruit snacks on the plane--she is quiet while she is chewing!! She will survive one day of eating just snacks-and believe me, it is a small price to pay to keep everyone (including your fellow passengers) happy.
Nothing worse than sitting next to an whining, screaming, unruly child on a non-stop to L.A.--I was the "other passenger" on that one. Never forgot that, and, now try to always remember my fellow passengers!