In the original trilogy of novels by Timothy Zahn, Grand Admiral Thrawn is a legitimate strategic genius who keeps winning until the heroes manage to squeak out a final victory by finding exactly the right flaw in his plans.
In the Ahsoka TV series, Thrawn mumbles vapid syllogisms that only sound profound if you listen to the tone of voice instead of the words. He constantly makes basic Evil Overlord mistakes and oversights, and only achieves the barest minimum success in the end through plot armor and luck.
It's like they're two different characters.
I'd say it's how the Imperium swallowed up and destroyed a number of civilizations that had separated from them that had been developing in much more progressive, prosperous ways. The Olamic Quietude and the Interex come to mind as examples. They showed that humanity didn't have to go down the terrible path they've ended up on.
Or, going farther back to look for a single "worst thing" that's had the greatest awful knock-on effects, I'd say that'd be the Old Ones' refusal to grant any aid to the Necrontyr when they asked for it. That one selfish act sparked off the War in Heaven, created the Chaos Gods, and everything that followed.
If you can't find the books available through legal channels in your country, you might want to consider looking for them on the high seas. !piracy is a good resource for that sort of thing.