Lifehacker just posted a travel tip on picking seats most likely to stay empty at the time you buy your ticket, but I've found I only keep an empty seat next to me about a quarter of the time using that method. There's a much more successful way to get what you want and I find it works about three quarters of the time.
When you arrive at the airport, make a beeline for the electronic check-in kiosk and skip the humans if you have a choice. When checking in via kiosk, be sure to hit the Change Seats option. Then do what the lifehacker post says, which is select an aisle or row seat with an empty middle next to it.
The chances that someone buys the middle seat after you reserved your ticket weeks ago is much higher than the chances that someone selects that middle seat in the last hour or two before your flight. Of course, this works only on non-full flights that don't happen during holiday season. I'd say on average weekday flights I almost always get an empty seat next to me and it's only on end-of-weekend return flights with tons of standby passengers that I don't get the extra space.