So I've had this problem with Nestopia. I have two Xbox 360 controllers that I've configured with it. I didn't like the fact that if both weren't on, Nestopia would have a popup saying "One or more joysticks is not connected would you like to remap?" And no matter if I clicked Yes or No, it'd erase my config. So I set the .xml file to read only. That helped and I even managed to get rid if an annoying popup when I closed it saying "Can't save the configuration!" by copying a ePSX ahk script I found online.
So what could I do to get rid of the popup "One or Joys