apt-get autoremove is almost always safe to run, especially on a single-user system where you know what software is installed.
But, there are scenarios where running apt-get autoremove could cause problems, for example: if software you’ve installed, or someone else sharing the system installed, depends on packages being auto-removed by apt. This could happen if software was installed from GitHub, for example, instead of using apt or dpkg.
It’s best to first review the list of packages being auto-removed instead of blindly running the command.
@markd Do you have thoughts on this?