Oh, I'm quite comfortable doing that sort of diddling.
Thanks for the pointer.
But my main concern is that I didn't do any sort of similar manual tampering to cause corruption of any kind. This is a fairly new/clean install of Calibre 5.3 with no 3rd-party plugins installed. I just configured an external app to open EPUBs through the usual Calibre Open With configuration interface. *shrug* But a fixed bug is a fixed bug, I guess.
Can confirm that a manual cleanup of the windows_open_with.json file got me back in business, though, thanks.