I've not been running it for very long, so I can't comment in depth. But, installing packages is easy (guix install), updates are quite easy (guix pull && guix system reconfigure /etc/config.scm) (but it is an unstable rolling distribution so sometimes updates need to be pushed along with --keep-going if they fail). I'm using EXWM so I can't really comment on DEs but it has Plasma, Gnome, XFCE and a few others so it can be quite familiar.

A nice thing about updates is that you can very easily roll back to a previous point in GRUB. Whenever you run system reconfigure it puts a new point in that menu.

I haven't used Flatpak so I can't comment.

The only thing that might be annoying to some people is the kernel it uses by default. The mainline Linux kernel, which for some reason permits proprietary blobs, is not used. Linux-libre is used, which kicks them out. Which means if you don't have hardware that has been fully freed, you'll have problems.

I believe mainline Linux can be installed by changing some things in the system config and adding an extra repository, but it'll build by source instead (since Guix is a build-from-sourve distribution with transparent binary substitution where they are available). And of course, then you'll make the de-facto GNU system run proprietary software. Which is certainly an odd thing to do, but if your hardware requires blobs to run then you unfortunately don't really have much of a choice.

Oh, and that's another point. You configure pretty much everything in config.scm. Users, kernel arguments, etc.

You can also use the GNU Hurd kernel if you want, but unless you have very specific hardware it won't work because of the lack of drivers so for most people right now that's meaningless.

It's not really a distribution friendly to new users, but I'd love to see it succeed. Maybe I'll write a nice installer and package manager GUI for it in the future?