Hi,
To your questions:
1) The "free air distance" between analog and digital dies not matter much here.
* radiated noise won't care much about a mm more or less.
* coupled noise mainly travels via GND. Thus you need a good GND concept.
2) Is there a second question?
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Ground concept is the key to a low noise audio circuit.
* you say
The board is 2-sided and the whole bottom is a ground plane.
.
When you have traces within a GND plane it is no GND plane anymore. Since it is cut into pieces it just is a lot of copper, but not much better than traces.
There are many discussions about GND planes (and "copper pour") here in the forum.
* one GND concept is " GND star point" wiring. In your case there are several sources of GND current: Two supplies, each audio input, each audio output.
True isolated designs are very difficult, thus one needs to connect these GNDs somehow. But when connected you can't control the (magnitude) of the GND currents. Switch mode wall warts will cause high frequency GND current, connected audio GNDs may cause GND loops, maybe resonance at some frequencies.
Thus having several GND connections (with big distance) on a PCB will cause GND current travel across the PCB. Even a true GND plane will cause voltage drop (audible noise) and coupled noise into signal traces...
Instead of keeping GND connections far apart, I'd rather put them close together to avoid GND currents across a wide area.
Better do all the GND connections on a separte star point - not on the PCB. Just feed one single GND to the PCB. Or feed two seperate GND (noise free for audio, "noisy" for power supply and digital part) wires to the PCB, but then these two GNDs must not be connected on the PCB. If you need to protect both GNDs from accidentally drifting apart, then use two anti parallel diodes to connect them. This limits the voltage difference to +/-0.6V.
* the dpot (control lines) could be easily isolated with optocouplers. Generate the dpot supply from the analog section supply.
* use bulk capacitors. Use fast ceramics decoupling capacitors at each supply pin of each IC/ module.
There is no single "correct" solution. All is "requirements" and the "compromise" to fulfill them.
Every designer has it's favourites. Several concepts, endless discussions....
Added:
About distance between analog and digital signals: Coupled noise not only depends on "distance" but also on "length" and "orientation".
Thus - wherever poissible - I feed noisy signals in 90° to the sensitive signals.
2 Layer: a low noise 2 layer concept is far more difficult and needs much more experience than on a 4 layer PCB. So don't be afraid of using 4 layers.
Klaus