Having just written up some thoughts on how you could do it I realize they wouldn't work, because I imagine you're presenting a "standard"/FHS-esque view of the filesystem to the non-nix packages, i.e. they expect a `/usr/lib/libssl.so` to exist. Whereas Nix's ability to strip away runtime-unnecessary packages comes from packages only ever using explicit absolute references to each other.

I guess a "third way" might involve using e.g. pypi2nix, bundix, node2nix and the like.