One time I was debugging a problem for a user of our desktop software (I work on https://expo.io) by sharing his screen and taking over his computer. And it turned out the reason the user was having problems was that in his /etc/hosts file, he had an entry pointing localhost at the IP address of some other computer on his network. Crazy. I have no idea how anything worked on his machine.

Took a while to track that was down. Was both bewildering and sort of satisfying to figure it out in the end.