For my most memorable antagonist, I probably have to go back to 1st edition, when I was running a campaign during college. The players were low level (2-3) and the antagonist was Hkut, a goblin fighter/magic-user. In a time when classed monsters were rare, Hkut stood out. He dressed in fine martial clothing and had an air of confidence and authority about him. He wasn't used to being disobeyed, and he had no problem using deadly force to make his point.
When the PC's had surrendered to the Hkut's goblin forces (after a long, drawn-out battle) and one of the characters refused to relinquish his weapon, Hkut cooly forced the issue with a Burning Hands spell.
To make a long story short, the party managed to escape, but they couldn't forget their humiliation at the hands of the cocky, 4' tall goblin. They returned to the temple and managed to catch Hkut in the open with few reinforcements. The battle was furious, but the party had the upper hand. As Hkut's life hung by a thread, he took one last action - one he had been saving for just such a moment, and one which embodied his spiteful disdain for all non-goblins: he cast a ground-zero fireball. The explosion killed two of the party, destroyed his own spellbook (which the mage had been drooling over), and destroyed several of the party's own items. Even in defeat, Hkut had managed to humiliate them.
That was freshman year, but the group talked about Hkut with loathing and grudging respect until the day we graduated. He had truly come to life in their eyes.
*wipes tear from his eye*
Anyway, for whatever reason I haven't had a villain since Hkut leave quite the same lasting impression as that cocky little bastard.