I'm the happy owner of the Axe I/O, running quite a few (standalone) plugins, of which some I hook up with output 3-4 on the rear. All four speakers routed through Cakewalk sound awesome.
According to the manual, the Master controls the volume of output 1-2, but I can't find a way to control the volume of output 3-4 other than through the slider of the Control Panel's Interface.
Unless I'm overseeing something, a similar knob on the Axe would be needed as now a computer screen is inevitable to controlling the level.
Obviously the mixing in the DAW has sliders for both stereo front and rear outputs, but are now 'depending" on the CP's Interface settings of 1-2 and 3-4.
Maybe the Master should have been (programmed?) an 'overall' output 1-4?