Columnaris. Wiped all but two fish from my 30g betta sorority plus a few other things in there. Mind you this was my second (failed) attempt at a sorority (first was a mix of disease knocking my stock number out of whack and being too broke to fix them), and all the bettas had been a birthday gift from my boyfriend.
I had a guppy and my diehard BN make it out, the BN is still kicking and that guppy's genes are still kicking in the stock I have now
There was the time I came home to the blizzard of fish food in my tank after vacation, lost the baby fire mouth that took me almost a week to finally find something it would eat and almost all my cories ( had an over zealous uncle feeding them).
The convict that did nothing but literally shove itself in a hole in the driftwood all day, only to come out and murder (but not eat!) the danios I got as dither fish so it would feel safe to come out...
The pictus who killed (but again did not eat!) the guppies I gave it, and who beat the ever lovin crap out of my once gregarious BN. The BN had never been the same since btw. It's been 11 years!!
The platy from hell that persistently tried to eat the eyes off of my ADFs in my one attempt at a 'traditional' tropical fish setup.
So yeah, the sad times happens.