I haven't had any huge disasters, but the toughest loss I experienced was probably the first one... When I was 8-9 years old I got my first tank, and I think we were moving it or something? We had all the fish in a bucket, and one of my zebra danios jumped out. I found him on the floor, and he was a goner... But I thought that my mom should be able to do something to help him because she is a nurse. I was devastated...
Not much of a story... But it was crushing at the time.
I was also pretty upset when two of my brookies jumped out of their tank the day after collection. I had used shade cloth as a cover, that was a mistake... The first thing I did after finding the two dead fish on the floor was go out and buy plexi for lids.
The rest of my fish disasters have been more wet floor related... I use RO water and fill 5 gallon buckets, and I uses to leave the bucket on the floor and run a tube from the faucet. One time I went outside to pull some weeds and my wife came home to find the bucket overflowing and the kitchen floor soaked. She just about lost it and suggested that all of the tanks had to go. That didn't happen again... And the stupidest part is that the bucket fits in the sink under the faucet... So sometimes I still forget it while it is filling, but it overflows down the drain.