It depends if you’re carrying the keyboard with you or not, if you’re using it (for example) with a laptop where you sometimes want to use the built-in keyboard, if you’re able (permissions-wise) to change the layout in the OS, etc.
If you’re carrying your keyboard with you, it makes sense to customize the heck out of it, including any alternate keymaps you use, so that you can plug it into any computer that’s expecting to get QWERTY, and it “just works”, without having to change the OS on multiple computers, some of which may not belong to you.
If you’ve got a laptop or other alternate keyboard on the same machine (that’s not customizable), that you want to use with a non-QWERTY layout, it makes sense to let the OS do the layout mapping, and configure your Model01 as I described above, so that it does what you want after the OS applies the layout mapping.
If you’re not able to change the OS keymap settings, then you want the mappings done in the firmware.
If other people need to sometimes use your computer, it’s nice to have the OS set to QWERTY.
For example, I backed at the 2-keyboard level.
My Model01 for home use, which I’ll be using primarily with a desktop and occasionally with either a MacBook Pro or a Win10 laptop (which may learn to dual-boot to Linux), is configured to assume that the OS is handling Dvorak mapping. Note that this doesn’t stop me from using the extras that Kaleidoscope provides, it just determines what keycodes I use in my layout - essentially, for the punctuation keys, I need to do the inverse of the Dvorak mapping, so that when the Dvorak mapping is applied, I get the correct key.
My work computer, however, is set to QWERTY at the OS level. I’ve got the keyboard that came with it available for others to use - for example, if we’re pair-programming at my desk. That board sits on the back of the desk most of the time, while I use a board that has the Dvorak mapping and other customizations for my daily driver. Currently, that’s a TEK (Truly Ergonomic Keyboard); once I get my second Model01, that’s where it’ll live, with a natively Dvorak keymap & my other customizations I’ve worked out on the first Model01.