I tend to fly Southwest, which is great because I can choose who I set near and next to. For long flights, I'm looking for aisle (so I can get up and walk around), for short flights a window to look out of. Other than the window/aisle thing, I just find an area of the plane with no groups that look noisy (children, school groups, frat boys, etc.) and sit by people who look small and quiet.
Last time I had to fly non-Southwest, I pre-selected an exit-row window seat. Unfortunately, the guy next to me turned out to be well over 300lbs. Kinda negated any extra room from being in an exit row. Just emphasized that I prefer picking which people to sit next to more than picking a specific part of the plane.