Not a death, but a ragequit.
After a rough start, my fledgling star empire was finally getting itself together and expand outward. We had been under the "protection" of a pirate band while we were getting on our feet, but once FTL was invented by my people and I had something resembling a fleet in operation, I broke the protection agreement. I figured I could handle any random pirate frigates that decided to make mischief.
The first problem was that several of my worlds had pirate strongholds on them thanks to their long influence in my region of space. They had to go, so I spent large sums of money raising army regiments on each colony and ordering them to attack the pirates. They put up strong fights, but I couldn't keep much of an eye on the battles because I received word that two of my newest colonies were being raided.
I check on them and discover that the pirates, damn them to the Abyss, had managed to scrounge up a couple of ancient cruisers. These things were massive, and filled with tech several generations ahead of my own despite their age. They easily swept aside the local defenses and began to plunder and pillage, leaving long before any of my reinforcements could arrive. When the reinforcements returned to their own ports to refuel and refit, the pirates returned to those same colonies to launch further raids.
Meanwhile, my attacks on pirate strongholds had mixed results. Several strongholds had been destroyed but others had held, requiring the training of additional troops to replace the ones lost and try more attacks. This took time, and all the while further raids were launched. One of the raided worlds even developed their own pirate stronghold, mocking me for being unable to stop single warships that could outfight my entire fleet.
Eventually the pirates offered a new protection agreement, and despite the large increase in monthly fees I took it. The massive pirate cruisers just sort of...hung out, not moving or doing much of anything for a few months while I began trying to rebuild.
Then the pirates resumed their raids without warning. One of my best research stations, deep inside my territory, exploded due to sabotage and killed my best scientist. I attacked and destroyed one of the last pirate strongholds on my worlds. Immediately afterwards, almost as though the pirates were responsible, a massive plague broke out on that same world and began spreading to others.
I had had enough. Quit without saving, screw you very much game.
Distant Worlds: Universe. I love this game, but when it decides to rough you over it will never ever stop.