Narrowing it down to just one is pretty tough, but if we're discounting the Angel series, and I had to pick only one, I'd have to go with "Passion" from S2.
More than any other from any season I think, that's the episode that really dials everything up. The stakes get raised more than they ever had been, and the entire complexion of the entire show gets hugely altered. Angelus suddenly becomes THE villain of the entire series, and we go from wondering when the old Angel is coming back to seeing him become a sadistic monster apart from anything we'd seen on Buffy before.
Plus, it's just an awesome episode. The ending is fantastic. Angelus not only killing Jenny but laying the trap for Giles to find her was one of the most chilling moments of the series and for the first time we see an entirely new side to Giles when he cowboys up and storms the factory. On the lighter side, the chemistry between Angelus, Spike and Dru is hilarious. Plus, Angel's narration adds an incredible layer to it. I love, LOVE, this episode.
There are a lot of episodes that I came close to picking. "Becoming", "Surprise", "Innocence", "I only have eyes for you", "Band Candy", "Graduation Day", "Pangs", "The Gift", "Grave" and "Chosen" are all amazing, stand-out episodes that I never get tired of. And there are a number I left out. That isn't even touching on the Angel episodes (which I think the best of are just as good, if not better, than the best of Buffy).