In my various campaigns, I would say that the toughest opponent my players ever faced was Orcus, in my (heavily DM modified) Taladas campaign. Orcus has always been my favorite of the demons and devils, being the Lord of the Undead. I make him very powerful! I believe we faced off with him twice. At one point he had been summoned to the Prime Material Plan and took over an evil kingdom, intent on spreading his reign. In that battle, I remember losing near 100 followers (we had plenty of PCs and NPCs and they rolled rather well when rolling up followers), a handful of PCs, and a handful of NPCs. It was a near TPK, and only the use of a powerful relic and some semi-divine help allowed victory.
Other extremely powerful encounters (in other campaigns) included (in a FR campaign) a run-in with Szass Tam, which ended in a lot of death, and another with Halaster in Undermountain (in another FR campaign) in which he allowed the adventurers to live, but devastated the entire party and destroyed almost everything they owned. Turned some of the party against the others and laughed his ass off while they killed one another. He also thought it was hilarious when the PCs tried making it out of Undermountian (from Level 3) without any magic items or weapons of any significance left intact.
