The default layout (mostly QWERTY, but split ortholinear) took a week or so to learn and has been totally fine. My only problem with it is that so many of the modifiers depend on my pinkies, which are my weakest finger.
Luckily, the default layout maps control as "hold Z key" which means my pinky doesn't need to travel as much, but it still leaves me with a sore pinky. I'm thinking of mapping a key like "O" that gets hit with a stronger finger like my ring, but inertia is great when changing a habit you've developed daily.
One thing I'll say about the ergodox is that you really notice it's value when you go back to your e.g. laptop's keyboard. Whenever I use my T495, I immediately notice that, while my typing speed is higher, it's putting a far greater strain on my hands and wrists (and back!)