Mario's return, and his subsequent attempts to return Mr. L to normal.
Badman Vegeta's transformation into Maijin!Vegeta, upon which he devastated Waluigi in Singles competition and proceeded to turn his back on and beat up Nappa. The chat room was crushed.
Much like in the source material, Majin Vegeta throws off his mind control, and challenges Dracula. He loses, but decides to take Dracula to his end with him. What makes it even worse? Dracula survives.
Fortunately, similar to the source material, Nappa has found some Dragon Ball locators from Bulma (after breaking her legs) and is going to attempt to bring Vegeta back from the dead. The only problem is he got quite a few spares — and he left them out in the open for Wario, Waluigi, Gaben, Jensen, Eggman, and Wily to get.
The ending of the June 20th show: Bryn McMahon has been fooled by Carmen Sandiego and betrayed by Mavis Beacon and is dragged off by the cops. The final shot of the show is a small animation Bryn looking defeated as he is driven away while a somber remix of the credits song plays...until he escapes.
The beginning of Zangief's utter shock that Ganondorf has broken their team, as well as having to accept that Ganondorf has no remorse for what he's done, and is now full-on evil.
Protoman's death by the hands of Air Man and Knuckles. His demise actually causes Knuckles to feel tremendous guilt, and gets him to rethink his partnership with The Practice. Towards the end, he seems to be gathering his remains for a proper burial...or perhaps something else?
It's possible that Knuckles might've handed Protoman over to Gabe, who, while not exactly known for his genius in VGCW, is also developing the very powerful and promising Steam Box console out of universe, and Gabe hinted at Protoman returning by End Game 5. This might mean Protoman will be getting a redesign, which might finally get him to shake off the boots of his "Glitchman" reputation.