I have a Presonus Firefox 2 channel stereo preamp and Mac Mini. I got it
working ok out of stereo speakers using Garageband and Mini Moog V.
Using the Presonus allowed me to have a higher quality soundboard over
the built in Mac soundboard chip.

But, I was wondering:

How do you get stereo speakers to work while hooked up to
the Firefox to play internal Macintosh applications, such as the
games that came with the Mac? Or, if I purchase a flight simulator,
how do I get the sound to come out of my stereo speakers?
Right now, I find myself having to use stereo headphones hooked
up to the Mac Mini headphone jack, to hear the output of a game
program.

In other words, is there some kind of setting I have to configure
on the Mac to get it to work with stereo speakers (other then
Garageband or Mini Moog V)?

Thanks for advice on how to do this!

I think you mean FirePod, not Firefox?

Select FirePod from the System Preferences -> Sound to make it the default device for system sound.