I run Home Assistant from a "manually managed" Python virtual environment as well, and have been doing so for years. It works fine. The developers are quite aggressive in insisting on recent Python releases, so upgrading is always a bit of work, but it's manageable. I'm using supervisord to keep Home Assistant (and AppDaemon) running, but you could use systemd as well.

Sounds good, thanks. Running manually for the time being, I did see the deprecation warning for Python 3.9, meaning I should get around to updating this Raspberry Pi to Bookworm. (Or NixOS, like my laptops, then I can manage things with more granularity.)