Given my limited usage of system themes to one that has flatpak packages (Materia) and tendency to go through the permissions of new flatpaks and tighten them anyway, those are good points to mention. For theming, it is definitely a trouble point depending on the platform and theme used. Especially when combining Qt5/Qt6 apps, Fltk, GTK2,3+, and GTK4 applications together, things may get even more messy than consistent theming on native applications. Having comprehensive theme packages for the theme you use almost completely resolves this problem. Though I doubt predefined customization isn't something that will be popular with some users given that ricing your Linux desktop to the extreme is a huge selling point of the Linux desktop for many.
I did forget about how especially with Flatpak and Snap how there is no actual guarantee that the default sandboxing permissions will actually be any good or even usable on many applications, which is an issue that partially comes from when community maintainers end up publishing packages for developers rather than developers or dedicated platform testers publish a given package (a common practice for many applications on the Flathub repository).