For me, I think Emperor Riesstiu (Homeworld) destroying the planet Kharak (Where the Hiigarans/Exiles were forced to flee to) and then publicizing the fact, triggering a rebellion that... well, reamed his empire. Badly. I mean, You have these Hiigarans who have forgotten who they are, they have this small, nearly staggering fleet, and they overtake an Empire that had been in undefeated rule over the galaxy for literally thousands of years, all in a period of six months.
Nice going, Riesstiu. You're an idiot.
If you have no idea what I'm talking about, you can read Homeworld's storyline at the Homeworld Shipyards.
So, what do you think the dumbest thing an antagonist/evil empire has done in a video game?