I almost created a topic regarding the same problem with Retroarch yesterday.
For me, Retroarch has responded haphazardly to controls. Sometimes they work, sometimes they're completely unresponsive. I've been using Retroarch for more than a year on various platforms so I'm pretty familiar with it and here are the things I've tried:
1. disabled auodetect for the controller
2. manually bound the keys (this always works fine)
3. cleared the data and cache from the app manager
4. uninstalled and reinstalled the app completely
5. disabled "use global settings" in the settings
6. tried changing the IME and then changing it back
7. rebooted the deivce
8. complete power down and reload
9. changed cores, tried loading a new game
10. deleting config file
Also worth noting is when the controls don't respond in-game, the on screen back button doesn't do anything either. You can see the animation for it being pressed, but nothing happens. Also when this is going on if you try to load a new game, it looks like it loads, but then you're thrown right back to the game that was already running and not responding. This has happened regardless of core or game selected.
Something else worth mentioning is that on the OUYA, I have seen similar problems with Retroarch, where it stops recognizing button presses on the controller. However, the problem happens MUCH more frequently on the G5A. I also considered posting about it on Retroarch's forum but didn't since there are a few similar posts with no working solutions.
If anyone has run into this and been able to come up with a solution, I'd appreciate it.