I ended up with pretty much my own entire layout. For the most part, I don't use layers, but instead use pairs of keys for symbols, numbers, etc. I also kept things largely where they are on a traditional keyboard, so that I'm not fighting against several decades of muscle memory.

The main issue with what I've done is that I'm kind of pushing past the limits of combining features with QMK. I use pairs of keys as modifiers (my left shift is 'E'+'D' for example), this key pressed is also '3'. If I roll on numbers, I end up with stuck modifiers. I've gotten fairly used to it, but it still hits me from time to time.

I do use a layer for things like cursor keys, though.

Isn't it great to make your own design that has the features you want in it. I found myself wanting a lot more aggressive stagger from what is common (my 'Q' is a full key-length down from where 'E' is. I mostly came up with by just looking at my fingers.

To mirror another commenter, perhaps consider doing a PCB next time. I did it after my first build, and am very happy with the result.

Using an ergo keyboard (ultimately my own design, but starting with a Kinesis) has really helped my wrist pain. I ended up making sure portability was part of my design, because I found that using my laptop, even for a fairly short period of time, makes the wrist pain start to come back.