Defeating Oryx The Mad God 2. If you can land the finishing blow, you have officially won the game.
Even more so if you get some incredibly good loot from him.
Managing to beat a high-level dungeon like The Shatters, or one of the Boss Dungeons like Shaitan's Lair.
Hell, soloing any high-level dungeon or boss will make you feel like a badass. It's even better if it was a dungeon or boss that previously gave you trouble.
That Ent Ancient that almost killed you when you were Level 9? Now walk up to it and utterly annihilate it using your new max level or UT weapons. The Undead Lair you could never seem to beat? Rampage through the whole thing without taking so much as Scratch Damage and crush Septavius with his own Doom Bow.
Nexus'd with <100 health at max level with good gear. After being surrounded by a swarm of Realm Gods or other Beam Spam.
During a lag burst
WITHOUT an AutoNexus mod
Getting a White Bag from a boss. Even more so if it is actually a good item, is incredibly rare, or comes from a difficult boss like an Event God.