So, the points in favor of Kinoite is sticking closer to upstream, however it seems like I would need to layer quite a few packages. My understanding is that this is discouraged in an rpm-ostree setup, particularly due to update time and possible mismatches with RPMFusion

It’s not only discouraged but often times it’s system breaking. I used Kinoite for a year before I just became too frustrated and gave up. The first thing I learned though was to stay away from package layering because it tended to break things more often than not. Basically if you can’t find or build a flatpak and you don’t want to use toolbox all the time, just stick with workstation. Immutable is great when deploying to multiple servers or locked-down corporate workstations, but it makes no sense for your personal setup especially if you’re already familiar with Linux.