When Anet finally decided to nerf the champion train in Queensdale - meaning players would finally be able to explore the zone without being run over various bots, farmers, and power levelers in the neverending Zerg Rush.
The final confrontation against Scarlett Briar. After she uses an explosive that leaves Marjory out cold and burned with Braham limping from injury. Rox can only tend to them due to the severity of Marjory's injuries..leaving the player and an enraged Kasmeer to team up against her. Kasmeer puts her illusionary magic to best use screaming death on Scarlett, allowing you to get in and strike her down before dealing the final blow and putting an end to one of the most notorious villains in player mind considering what she did to the main player hub, Lion's Arch (Which still hasn't been fully repaired nearly a year later).
The end of Dragon's Reach: Part 2 involves the Player Character going up against the Shadow of Mordremoth and driving it away. Alone. In other words, you beat Mordremoth's equivalent to the Shatterer, Tequatl the Sunless, and the Claw of Jormag all by yourself and live to tell the tale.
To make it even better, your character explicitly compares it to Blightghast, the champion of Zhaitan that took over Claw Island and required the combined efforts of all three Orders to take down. This time, you're stranded alone with the dragon. And you win. But the real kicker? Blightghast also killed your mentor. In a roundabout way, It's Personal.