I remember observing my colleagues who had spent like a day troubleshooting an issue. The root cause was one end of a link sending super jumbo frames, which the other one was not configured to accept.
It may sound simple but it was pretty hard for them to reproduce.
Pretty good if they did it in a day. Encountered the same issue and it took me at least three days to resolve. The issue presented itself as a database table not updating.
It was three to four people who were poring over packet analysers, so probably a similar number of man hours.
Once you've seen it happen you think to check for it pretty quickly.
For me it was network going down after maximizing SSH console window :D