Without a doubt, Angel/Angelus was, to me, by far the most diabolical villain that Joss ever came up with. This is, not just a bad guy, but THE bad guy, set on destroying the world as we knew it. Nothing particularly special about that, really, and he most certainly wasn't the most powerful opponent that Buffy would ever face. What made him so special, so difficult to defeat, and what cost Buffy the most to achieve that defeat was one unique thing. Buffy couldn't look at Angelus without seeing the man who she loved and wanted to spend her life with. She never felt that with the Master, Mayor Wilkins, Adam, or Glory. By the time that Dark Willow came along, she was obviously mature enough to handle the similarity of the situation, but for a 17 year old girl to have to kill her First Love, that must have seemed as though, in order to save the world, she had to destroy the most important thing in it. I would compare the shock of such an event to be almost comparable to Angelus or Spike suddenly regaining their souls, and it says a lot for Buffy, a teenaged girl, was able to retain as much of her sanity as she did.
Second on my list (I know that you only asked for the one worst, but I'm on a roll here) would be Glory, because she was the first opponent that she ever faced who was so powerful that she could have squashed Buffy like a bug, and probably would have, except that Glory saw her as the only way to find the Key. And, speaking of the Key, once more Buffy was put in the position of directly protecting someone who she loved from direct harm from the Big Bad.