Identify your specific needs in airline seating--what makes an ideal airline seat differs from person to person. For instance, if you are tall, you will likely want an aisle seat. On the other hand, if you suffer from motion sickness you may want to choose a window seat so you can see the horizon and lessen the sensation of vertigo. If you know you will need to use the restroom, an aisle seat will be easiest for you, but remember that you will also have to stand up to allow others in your row to use the facilities. For a long flight, or a redeye, the window seat might be better so you can get some sleep.
Consider an upgrade. Some airlines offer business class seats at a reduced price or in exchange for miles. It may seem like a high price to pay, but if you're embarking on an especially long flight, a few hundred dollars might be worth arriving at your destination rested. If you sign up for frequent flyer programs with the airlines you fly most often, you will be more likely to receive upgrades when they are available.
Compare seat dimensions and pitch. Not all airline seats are created equal, and not all varieties of plane have the same seating arrangements. Utilize a resource such as SeatGuru.com or SeatExpert.com to research the size and pitch of the seats on flights you're considering. Pitch, or the distance from a seat to the one in front of it, is especially important if you're tall or long-legged.
Exit into comfort. If you need extra leg room, you may want to request an exit row seat. Be aware that if you are traveling with children, you will not be able to select an exit row for the whole family. People seated in the exit row must be willing and physically able to help in case of an emergency, and generally have to be age 15 or over.
Strategize when it's warranted. Take a look at the available seats on your flight. If you want to be seated next to an empty middle seat (and really, who doesn't?), look for rows where someone is already seated in the aisle or window seat. Otherwise, a couple traveling together will be able to reserve the two seats next to you, ending your dreams of piling magazines in that middle seat. You may also have more success in securing an empty middle seat row if you look to the rows in the rear of the plane, since most people prefer to sit in the front.
Book early. You'll have more options available to you if you book your flight as far in advance as you can.