Maybe this will help answer my specific case.
The computer I'm using in my arcade cabinet IS NOT hooked up to the internet. When I ran Daphne Loader, it always started up with two errors/pop up windows. I think one said something about not being able to go online to check for something. I would click ok, and then another popup mentioned not being able to update the controls, probably also because it couldn't go online. Clicking ok at that point started Daphne Loader ok. And my remapped controls were definitely in there. They just wouldn't work once I started up an actual game through Daphne.exe.
So hoping that was the problem, I downloaded Daphne again, and started up Daphne Loader on another computer, and it started up fine without any errors. I remapped the controls once again, and then I closed it and loaded it a few times to double check everything.
Then I copied my entire Daphne folder back into my arcade cabinet computer. But again, my remapped controls just wouldn't work.