Easiest is to tie a keyboard command to the master fader's mute button or similar but that doesn't work if Reaper doesn't have focus. Best is to have an analog volume/mute on your desk. That's what I have (Presonus Mix Station) but there are likely less expensive options.
To drive this home, there is nothing better than a physical "oh shit knob" that you can grab instantly. I'll never go back.