The problem is that _every_ _single_ _program_ has to have its configuration files rewritten to take nix or guix into account, and every sysadmin has to know how to use the new nix or guix way.
I don't think this is the case. I've packaged several things for Guix, and patches are rare. Stuff that has good configuration (e.g. uses GNU make, and thus accepts --prefix) will be fine.
I never really tried guix, but that's how nix works ( https://nixos.org/nixos/manual/index.html ). So how does Apache configuration on upstream (meaning, how it's configured on Windows/Linux/FreeBSD) correlate to how it's configured on nixos/guix?