The biggest problem Nix[OS] has right now is documentation. The wiki is deprecated, but still the only source for explanation of several key parts of the system. nix-shell is fantastic, but hard to learn simply because there is no specific place to learn. Nix language really needs some clear documentation so a user can understand how to get from "I don't have X" to "I have a working default.nix for X, and X installed in my environment."

GuixSD seems nice, but seems to have no method for installing non-free software, which is, unfortunately, necessary for many setups.

One thing I would like to have is a Nix/Guix wrapper for Debian packages (and possibly other packages/distros), so I could take advantage of Debian's robust ecosystem, and NixOS/GuixSD's totally functional environment.