I agree Nix being new/odd is a barrier, and that NixOS be more popular if the language was more popular.

Guix System partly answers this by using Scheme, but ultimately Scheme is unpopular too.

A NixOS built on a no-side-effects JS/Python (e.g. Skylark, used in Bazel) would be possible.

The build output, a derivation, is just a data type (~ JSON object), and so interoperability between NixOS and something else is possible.