No. 1: The Leader

Credit: Marvel.com
First appearing in Tales to Astonish #62 in December 1964, Samuel Sterns was exposed to gamma radiation just as Banner had been. The gamma rays however had a quite different effect. Instead of receiving brute strength, the gamma rays enhanced Sterns' mind to super-genius levels. Using his newly acquired intelligence for personal means, the Hulk just happened to be present at a time when Sterns, now calling himself the Leader, was stealing parts for a machine he was building. This was the first of many setbacks the Hulk would cause the Leader. After numerous setbacks the Leader refocused his efforts on finding a way to rid the world of the Hulk once and for all.
The Leader is truly the opposite force to the Hulk in every way, perfectly exemplifying the word "nemesis." Sending wave after wave of his creations to battle the Hulk, robotic war-machines or rubbery pink humanoids, the Leader used his intelligence rather than brute force to battle the Hulk and at times it was Banner who was forced to battle the Leader in a game of wits rather than strength. Perhaps the Leader's greatest triumph was during the Ground Zero saga where he detonated a gamma bomb that seemingly atomized the Hulk and transformed a small town populace into gamma mutates. A super-villain mastermind, the Leader has defeated the Hulk numerous times and has solidified his place has Hulk's greatest enemy.