I have DM'd a few. Off the top of my head, the ones that stick out:
1) vs the "Dragon of Doom in 1e/DnD:" The party quested for an ancient artifact to slay the all powerful dragon. The found it, confronted the dragon, and found out it was a fake - TPK. This was back in '89 or 90 when I as still pretty green, not my finest moment
2) vs ancient black dragon in 4e: The party unexpectedly encounter an ancient black dragon when they were level 7-8. They foolishly tried to attack it, quickly realized they were outclassed and fled. The dragon chased and they ran into a dungeon and the dragon was too large to follow. Thinking they were safe, they explored the dungeon. However, the dragon had one of its children silently follow them down into the dungeon. Eventually a battle ensued and the dragon was killed. Again the group thought they were safe when the whole dungeon began to shake around them as the parent tore through the ground to get to them. They escaped through a teleportation portal just before the dragon collapsed the dungeon on top of them.
That encounter got high marks from everyone with much discussion afterword, including plans to go back some time and take care of mama

For me, as a DM, it was nice to give them an encounter they couldn't fight there way out of and see how they handle it.
3) vs. Ashardalon in 4e: unfortunately I don't remember this one much. It was part of a one-off epic adventure (PCs all level 30) I ran will traveling in a van for 12 hours (wife and friends drove while i DM'd) and it was followed later on in the adventure by...
4) vs. Tiamat (heavily modified) in 4e: The PCs arrived too late to stop a ritual that brought Tiamat into the world with her full divine power. The PCS were at full power and so was she. There were 6 PCs and after 4-5 hours of combat 4 were dead, another was dying, and only one was standing to make the final blow to banish Tiamat back to the Nine Hells. Everyone had a lot of fun and it proved to me you could kill epic characters in 4e
