We fly frequently with our son and here are my keys to success. We get to the airport early so that we can have a worry-free trip through check-in and security. Then when we get to the gate we encourage him to run around, climb, do anything physical. We do a diaper change right before boarding time. I do prefer to board early because it makes it easier to find space to store stuff where I want it. And I am more likely to be able to get a blanket and pillow from the flight attendant. These things I keep under the seat in front of us: a small mesh bag with one diaper, a changing pad, and wipes; a bag with toys, snacks, and a small blankie or lovie. Everything else gets stowed in the overhead bin. I always bring some new toys and books and even wrap some in colorful paper so it takes him some time to unwrap them (anything to use up another few minutes). If the flying is turbulence free we always take one walk in the middle of the flight and it is nice if there are other kids so we can stop and socialize for a minute.
One more hint. If you have not flown lately I strongly recommend going to the TSA website and reading the list of items that are prohibited or need to kept in limited quantities in your carry-on. Having your quart size baggie of liquids and gels all organized and accessible makes security a breeze...and the TSA agents always thank me :)
Have a fun trip, most kids travel on airplanes with zero difficulties. My son is extremely high energy but we have only had one bad flight out of dozens. I've never even considered Benadryl and we've never even used a DVD player (although if I was flying more than 6 hours with him I would try the DVD).