[Suicide Junkie]

For me, I'd have to say the time under P&N, where I sent 200 battle ships plus a battlemoon to attack a huge breathable, rebel norak world.
I had biocrystal armored ships, but they had a full planet-load of massive APB platforms with talismans.

The fleet was wiped out, and the battlemoon sustained plenty of damage.

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Or, perhaps the game that my Exodus scenario is based on...
One little log message, and suddenly my whole empire is on borrowed time.
The stars go nova, and the whole hermit empire is reduced to nothing more than three tiny colonies, one unmothballed dread and a garrison of fighters.