I remember there being an issue with the combination of Real Guitar and Babyface before (with an older GP) — there was some bizarre interference as if the Real Guitar plugin was somehow screwing up the audio processing. I know you figured it out but I don’t remember what you did.
I assume you’re running the latest drivers for the RME.
Also — I have seen issues where anti-virus programs (including Windows Defender) prevent programs from working properly — even when people think they have been disabled, they still seem to interfere — maybe there’s a permissions issue going on.
I’m really sorry you are struggling with this — I know you have been a great GP supporter over the years and GP4 really should just work out of the box for you ---- we had a huge test cycle over the last year and certainly there are others using Real Guitar with GP4.