[dmurray]

For me the biggest problem is C-based python modules that can't just be installed in your virtual environment but want to be part of the global installation.

Tkinter and mpi4py are the most recent ones I've had this problem with. I expect someone will tell me "it's trivial to install these in a venv, just do X", but X is not obvious to me.

[fock]

it's trivial to install C-programs with the appropriate tools such as Nix and spack. You might end up in Tcl-hell in your new python-environment, but as it's not that widely used anymore, one should be fine.

Having said that: you generally want this packages integrated with your system (which provides a self-consistent Tcl as well as MPI-environment)