This is probably going to be opinion-based, but I only use 24 bit 48kHz for broadcast, let alone YouTube.
If, heaven forfend, Hans Zimmer or Skywalker Ranch rang me to engineer their next multi-million-dollar movie soundtrack, then obviously I'd reconsider.
Until then… 24/48k is good enough.
I'm curious about why you would need/want to do this as opposed to getting a voice actor to speak your lines.
There are a couple of approaches you can take to this.
The simplest is probably to apply some serious mangling to the voice using things like ring modulators or vocoders. These will change the voice so much that recovering the original voice from a ...
~~You could potentially silence the background voice only when the primary voice isn't speaking using a cleverly calibrated Gate. Another suggestion would be iZotope RX type tools, which I believe you can try on demo before buying.~~
*edit: my mistake! read too quickly and thought they were trying to eliminate the bg voice.
To amplify the bg voice, one could ...
Your computer sees the entire mixer as a single input device. But you will not be able to hear anything with the guitar on 2 because the 1/4” input is a line input not an instrument input. You will have to use a preamp.