I've used both SPD and LOOK pedals.
Coming from a background in MTB, I used to have SPD's, even on my road bike, but once I started triathlon training, I decided it looked a bit silly with the SPD's and finally caved in and bought some LOOKs.
Biggest questions to ask is "what type of riding am i doing?" and "what do I want to get out of riding?"
SPD's are definately the way to go if you're commuting or even on long leisurely rides. I did a 155km road race in mine and had no major problems (other than sore legs, but can't blame the pedals for that).
But, if you like the hills or if you're thinking of going into racing, it's hard to argue against LOOKs. The power transfer you get from the larger contact area will save you energy and keep your legs feeling fresher for longer. Even if you're in a hurry to get to work in the mornings, you'll probably find a bit more speed out of the LOOKs.
Hopefully this helps!