Couple that come to mind:
Agony Grind-just south of Rt 17 in NY before entering Harriman. The whole section from 17A-17 is a series of stiff ups and downs, but the ascent and descent over Agony can tire you out more than NY should.
The mile or so from the last Wildcat down to Carter Notch Hut was about as steep as it gets on the AT-my knees were screaming. As I recall, the climb outta the notch wasn't much easier (going up Carter Dome).
The descent into Pearisburg (northbound) was a knee-jarrer too. I've heard of a number of thru-hikers ironically injuring themselves coming into Pearisburg, its a bad luck spot of sorts. Maybe its just cause people are in a rush to reach town. It was at the end of a 25 mile mile, too-long day and I remember my feet throbbing.