What makes it such a good fit, in my opinion, is that the modifiers can be placed on the thumb clusters, and even layers 5 and 6 that otherwise require a combination of modifiers can have their own keys. On the other hand, having all control characters already mapped means you needn't find a good location for them anywhere. I still have 5 keys unmapped.
That said, getting used to the Moonlander took almost no effort at all for me, I was back up to speed in a few days.
In general, however, it is not a problem. Just remember, that adjusting yourself to a new keyboard is similar to learning layout and takes some time. If it is your first ortholinear split with a thumb cluster give yourself a week or two and then switch to other layout.
Why is that? Is it the productivity hit? Frustration?
At least for me, this will be at home personal keyboard, and I'll continue to use the work QWERTY keyboard for the foreseeable future. I might switch the work keyboard once I'm comfortable, but it's not a priority right now.
I also have another warning, based on my experience: it is for many people difficult to keep proficiency in QWERTY after they completely switch to Colemak or Dvorak. It is hard to describe: like you've been touch-typing on QWERTY for 18 years, and you know where the keys are, because if you look down, you immediately find them... but something is blocking you from finding them while typing. If you switch completely at work, find a week or two without much stress. New layout can be infuriating enough :)
I guess I'm a hybrid typist - I generally type only with my index & middle finders, but I can type moderately fast without looking at the keyboard. I had mild RSI issues but it might be the mouse usage.
I write small amounts of python code within an academic setting, so a week or two with low productivity is ... typical :)
You might move the punctuation even more central to really keep it 4-columned.
I use Colemak with my Kinesis split keyboards but that's irrelevant.
Keeping the C-c/x/v keys the same is great on a split layout, assuming you're right handed. I avoid using the mouse as much as possible, but when I do use it there's a good chance I'm copying or pasting something. With Dvorak you can't use those keys with your hand on the mouse.