Hi Scott,
thank you very much for your explanations and suggestions. Below my thoughts:
1. Use a high quality audio interface with ASIO driver support. I find the Behringer UMC202HD to have the best drivers. Steinberg is good. I don't care for the Focusrite, the driver stability doesn't seem very good, although perhaps it has been improved since I last tried it. Right now I'm using a Presonus, but it is very expensive and complex.
Thanks for the hint, I would need the UMC204HD, because I need the 48v phantom power for the Beyerdynamic Mic. I have read about the poor ASIO implementation of Focusrite, but I will give it a try (I have this device already)...at least, its worth a try. But the
Presonus AudioBox iTwo looks good
2. Attach the output of your audio rack to the input of the interface. Attach the output of the interface to your speakers and headphones.
Ok, in my case only the headphones, I don't use speakers at all
3. Dispense with the external mixer. Use Voicemeeter Potato. Put the interface on hardware input 1 and hardware output 1. Put PowerSDR (or Thetis) VAC1 on virtual channel 1. Put VAC2 on virtual channel 2. Put your digi mode software on virtual channel 3. Now you can mix and route audio to your heart's content all in software (it's very low latency), including mixing out some low latency sidetone.
The main reason for the external mixer is the quick and easy control. i.e. Watching a youtube-video (audio goes to headphone), on the side I am watching the waterfall (currently SDRConsole & RSP1), if a station of interest appears, I can quickly close the audio from PC (in this case from the browser) and make the qso and avoid transmitting youtube-audio

And all this without going into software, deactivating, adjusting audio.. I run 2 lcd-monitors, and both a filled nearly 90%

..no more space for additional panels... It is more a comfort-"thing" then a technical need.
Doing the mapping using Voicemeeter Potato is definitly a great idea for the audio-routing inside the pc.
I guess the Behringer Xenyx Q802 USB uses a similar USB-interface then the UMC2020HD, that would bring back the mixer

But if I look at my current setup (Yamaha MG06) the only knob I really use is the audio coming from the pc (see example "youtube" above)... I have to rethinking about that need. And if I am not wrong, listening to tx-audio from openHPSDR/Thetis could be a complicated job, because via headphone-out on a mixer, I would hear also the audio coming in from the mic....
4. Consider dispensing with your audio rack and using the built-in features of PowerSDR: leveler, rotator, pre-EQ, CFC compressor and post-EQ. If you use Thetis you get a fully adjustable noise gate/expander and look-ahead VOX, too.
Yes, thats the goal... I know the built-in audio-processing is second to none, and I want use that for sure.
And finally
"....audio-processing is also possible, when using VAC for mic-in/audio-out. But in the transmit-settings, there is only "line-in" and "mic-in" available. So I guess, that if no line-in/mic-in is present/connected and VAC is configured, openHPSDR takes the audio from VAC and processes it. Is this correct?...But what if there is also a VAC2 configured (ie. for digi-modes)... how to prevent the audio-processing from VAC2?"
I am right?
Thanks & stay safe
73s de Ernst
OE3IDE