I've found that I only really use two of the four keys on each thumb cluster, I suppose that's one disappointment, but I've just not found any modifiers worth the lateral movement. The main issues I've had are mostly self-inflicted, by repeatedly tweaking things and breaking muscle memory. I have no fundamental complaints, the only hardship at this point is that I can't always remember what symbol is above which number key. My current layout isn't particularly wild, I'm not a big fan of using multiple layers in normal operation, for example:
https://configure.zsa.io/moonlander/layouts/l79Bz/latest/0
With the ortholinear layout I've found moving P to the second row really nice, and you'll note I've squeezed the number keys inwards a bit. The central keys where I've got -/= and DEL/Backspace are important choices and I'm happy where I've settled. I've found this layout very friendly to my wrists and pinkies, and I'm comfortably back up to 90-100WPM. Takes some tweaking having space and shift the same thumb key on the right and I don't _love_ pressing the same key twice in a row to separate sentences.
Obviously these things are quite personal - I was looking for something Emacs friendly that didn't require thumb contortions for Alt keys. I had tried the X-Bows previously and found it an absolute disaster (don't put Enter next to Backspace, I'm far too clumsy). I've also settled on the toughest, clickiest switches because I only rest my hands on the keyboard and found I was typing by accident on every other keyboard.