Yesterday I had this sad adventure with UE4 when due to slow project load or some other reason I got it opened in 2 editor instances which I didn’t notice. To my dismay I’ve started to move assets between folders which lead to breaking references as some of the assets were opened in second editor instance and failed to save. Trying to open affected blueprints crashes the editor. This could be easily avoided if editor would allow itself only one instance per project. No point having two instances at same time anyways, is there?
Not sure if it counts as different projects, but I often have different checkouts of the same project open at the same time to merge Blueprint changes. (When I made some local changes while the asset was locked by someone else.)