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You never used anomic fedora. Fresh install is 6gb and with 68 flatpak apps it is only 20gb. Now compare it with non-atomic distros... I can help. 24gb Mint with 68 packaged apps could be 26gb? Or 40gb with flatpaks lol.
Uhm I do, daily since a year or so.
Most apps are slim, but needing 8 runtimes or so is nothing rare at all.
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Yes I have do the same, layer small packages, use Flatpaks and complex stuff like (R + rstudio + COPR + Modules) or (QGis + grass + python + plugins) or IDEs in a distrobox.
At least in Distrobox you can also create rootful containers which could run an entire DE, or run libvirtd in there and use virt-manager in a rootless box, connected over ssh. Totally works but its a bit complicated. But for software with systemd or USB access this is needed.
Flatpaks share libraries, but they are sometimes not packaged well, contrary to distro packages, which on the other hand may pull in loots of dependencies.
Would be interesting to run all packages in a rootful distrobox and have Fedora RPMs on the other hand.
There are some hardening problems though, that I dont really understand, with user namespaces being blocked in the hardened kernel. On Arch there is
bubblewrap-suidwhich fixes that in a way I also dont understand yet, but Podman, Distrobox, Toolbox, Docker etc dont work yet, and may not work too.