I'll start. Guess who the "Enemy" is.
This happened during my first game, when I heavily overestimated how good my fleet was. I'd recently encountered the Enemy four systems away, and I sent my strongest fleet of ~60 ships against their small scouting fleet of 3. Thousands of families found out about their untimely deaths an hour later... Yeah, I wasn't able to destroy a single one. The next few years only got worse as Enemy ships nuked my 13 outer colonies and their associated defense fleets. I was panicking since I was figuring out combat as I was going, and I'd only managed to destroy 3 of their ships in total, and only because they'd ran out of ammo. I'd already lost ~300 ships.
Back at my core 5 worlds where I had most of my industry and shipyards, I was trying to pump out as much cannon fodder as possible to slow down the Enemy armada. I was still noob at designing ships, so they were all bad, but the big ones, exceeding 100k tons, were the only ones able to deal any real damage. I had already made 5 of these new ones, while the others were taking their sweet sweet time.
In a surprisingly smart move, however, the enemy took a page out of General MacArthur's book and hopped across my inner colonies with their overwhelming power and numbers. While I was slowing them down, I was choking myself with a huge lack of every resource. By this time, I was still vainly hoping I could salvage the game and pull through, so I poured my remaining military into my two primary planets: Earth and Reach. The remaining skeleton fleets were easily destroyed by the enemy, and I patiently waited for them.
As I struggled to maintain the fleets, I tried to explore some JPs that I had ignored before and strip resources, but the Enemy was everywhere. Eventually a wormhole opened in Reach's system (What a coincidence, right?).
I prepared my defenses as, to my horror, a hundred Enemy ships poured into the system. The battle was lost from the beginning; my fleet numbering at around 600 was no match for the Enemy. But I still fought long and hard. As the Enemy burned Reach's oceans and forests, my ships swerved and cut through theirs. I'd destroyed dozens of them, but they destroyed four times as many of mine. Reach was lost in a matter of hours.
Despite their losses, the Enemy was relentless, and they quickly headed for Earth. They easily nuked Mars and my patrol ships, before attacking Earth's ships head on. The battle mirrored Reach's, and the last human breathed their last, soon enough.