I upgraded my laptop to macOS Big Sur the week it was released, which broke many things in nix and nixpkgs. I’d prefer not to make this mistake again! 
What is your experience running nix on macOS 12 Monterey? Are there any pressing issues we should be watching? How long should we defer upgrading?
I upgraded on Monday to Monterey and nothing broke for me so far. 
I was waiting with Catalina and Big Sur because of major changes in macOS.
It seems to work fine at least for the packages I use and in combination with nix-darwin.
Might also depend on the channel you use, I am not sure if there were things adapted during the macOS beta phase. I am running directly on master and that works fine.
I follow the stable channel when I can (only pulling a few from nixos-unstable). I upgraded to the beta of macOS 12 on my MBP several weeks before release. I didn’t run into any issues. macOS 11 was the big transition. If things were working for you under macOS 11, they should continue working under macOS 12. The only issue I’ve had was upgrading to an Apple Silicon MBP, which required pulling a few more packages from unstable compared to what I needed on an Intel Mac.
I also did a wipe and reinstall of Nix, so I can speak to the new install experience. You’ll need to use the Nix 2.4 release candidate if you want to install new onto macOS 12. Apple changed the error message the installer uses to identify a read-only root volume, so that fails on macOS 12, and the installer tries to create and write to /nix. Other than that, everything should work fine. I was able to install nix and then build my config and activate it.
Thank you for that addition. I totally forgot to mention that I am on an Intel Mac.