For a traditional package manager the drawback is that your version of python is now tied to your email client and can't be upgraded separately. As I understand it this is the value of NixOS, that one can have multiple versions of e.g. python side by side...

I don't see your point. On Debian, which has the most traditional package manager in the world, I can still easily install several versions of Python at the same time.

I'm not even sure what you mean by "your version of python is now tied to your email client and can't be upgraded separately". As long as the deps for each package are satisfied, either one can be upgraded.

My current Arch install doesn't have Python (because I don't need to), and I explicitly installed the same packages as in Nix.

This is just an example that some of their packaging policies are a bit odd, but they are working on this. Imagine using Nix on an embedded device. All those extra dependencies might make a difference in terms of resources used.

>My current Arch install doesn't have Python (because I don't need to),

That still doesn't explain why installing python is such a big deal for you, or why your desire to not install python is stronger than your desire to install mutt.