I believe they are suboptimal for the same reason that lexical binding won over dynamic binding in language design: it is easier to reason with immutable bindings, and to maintain as little global state as possible.

The work done in Nix and Guix is interesting in this regard.

I wouldn't say nix isn't anti-centralization, I'd say it's policy-agnostic. At the end of the day, not everything composes, only things whose interface is in some way compatible.

Traditional package manager conflate having something with composing something (everything is ambiantly available and interacting). Nix separates those, so you can have every version of everything, and only try to compose things that fit.

Because they impose a middleman between the application developer and the user.

I don't want a middleman, I want to get my programs from the developer, and store them using the tools I know (regular files on a filesystem).

Are package managers easy to use (most of the time)? Yes.

Are package managers (as they exist today) a universal, well designed way to distribute software? No, because they impose a middleman.