Honestly, this is the first complex illustration that I've done from sketch to finish in Affinity Photo (full rendered semi-realistic characters, 12"x18" @300ppi, a bunch of adjustment layers...). And it took me a while to feel really comfortable with the software. Why? My actual annoyance had nothing to do with the brush engine or the general speed (which is pretty good)... what really, really, bothered me, until the end, was the inability of flipping the canvas properly...
Let me explain myself:
In my regular workflow, I tend to rotate and flip the canvas A LOT! in Affinity Designer I have no problem at all when rotating the canvas, but unfortunately there's no shortcut there to flip it, unless you're only flipping one layer or the entire Artboard and if you have a couple of layers there, you need to keep selecting the entire Artboard constantly to flip the illustration vertically or horizontally.
Affinity Photo has the ability to do that, but unfortunately the graphic engine (or something) crashes and your image takes AGES to make the tile refreshing after flipping the entire canvas. So I felt very 'handicapped' during the whole process in that matter (I'll try to add a GIF showing this problem).
The brush engine and physics could improve (compared to Procreate or Clip Studio), I know, but I've managed to make them work very decently by tweaking a couple of parameters here and there.
Regarding the CMYK question, I never work in CMYK for illustrations for one reason: I use several blending modes and adjustment layers all across my layers and I have noticed that some of them don't work very well other than in RGB. What I do instead, when a client asks for a CMYK version is to make a flat version of the RGB and convert that flattened one to CMYK.
This conversation is getting interesting isn't it?