I got burned a couple of times having restarted a qube, and finding out that the agents saved information in a place where it isn't stored between reboots. I have a really good machine with lots of memory and storage, so I just by default now run full VMs so I don't have to worry about that problem. Maybe someday I will optimize more, but at the moment it isn't worth it to me, being a Qubes newbie and having ample storage and memory.

Persistence is a different parameter to template OS choice, you can have a minimal fedora machine that is a standalone VM with full persistence. Minimals are a clean OS without Thunderbird & Firefox etc installed. Saves you on storage and reduces attack surface drastically.