reboot or "systemctl daemon-reload" for changes to /etc/systemd/system.conf?

No, daemon-reload will reload all unit files, not the configuration for systemd itself. However, # systemctl daemon-reexec will re-execute systemd and cause it to digest its new configuration in the process.

From the systemctl man page:

       Reexecute the systemd manager. This will serialize the manager
       state, reexecute the process and deserialize the state again. This
       command is of little use except for debugging and package upgrades.
       Sometimes, it might be helpful as a heavy-weight daemon-reload.
       While the daemon is being reexecuted, all sockets systemd listening
       on behalf of user configuration will stay accessible.

When the man page says daemon-reexec is useful for package upgrades, it in large part means that this command executes whatever new binaries there are and re-processes its configs. HOWEVER, the RPM that we use to upgrade systemd already contains a script to do this, so it is usually never needed in the case of a normal upgrade.

Or you can reboot. Either will do.