IMHO, the most important things are:

1.) Chamois (get a good pair of cycling shorts)
2.) Fore-aft position of saddle - When crank at 90 degrees, should drop a plumb-bob from below kneecap and should land right over ball of your foot
3.) Stem length - not too cramped or not too streached out on the bike, should be able to ride comfortably with elbows slightly bent (no straightarms!)
4.) Handlebar height -- too upright is poor for aerodynamics, too low is tough on your lower back
5.) Cleat position -- under the ball of your foot, or slightly behind it.
6.) Saddle -- No saddle is one size fits all, you may try afew before finding a favorite. Don't blame all discomfort on your saddle until you have #1-5 above setup properly.