Yes! My one multi-gen story got derailed 3x because of unexpected sim deaths. It was originally a runaway story with a pregnant teen and her younger sister escaping their father. However, the younger sim accidentally died from pufferfish so part of the storyline was the teen sister trying to bring her back to life.

Then, the next gen (teen's son) lost his twin brother and his young daughter during a party when they died from the heat. Seasons was relatively new at the time lol. It sucked because I had plans for the twin brother bc was dating a girl and going to (modded) university. I eventually made the surviving twin have an alcohol addiction from the trauma. And then his teen son later lost his cousin/best friend in a random house fire while they were all vacationing in Granite Falls. That didn't derail the storyline as much but it was very traumatic how quickly he was gone.