As the subject says, I'm struggling to use the AXE I/O (input 1 or 2) with any standalone guitar simulation software (_, Mercuriall, etc.) while playing audio from Windows... this could be YouTube, Media Player, and so on.
I have a Focusrite Scarlett i8 on another computer and don't have this issue. I can use my inputs along with all audio routing through the main outs.
If I unplug from Input 1 or 2, I can restart the audio playback software and it will then play audio through the main outs. As soon as I connect my guitar input, the playback software craps out.