Yes, it is generally safe to edit all of your configuration files from the shell without harming the control panel. InterWorx was designed that way. It parses the existing config files for settings to allow maximum customization.
This does not, however, preclude some of your changes from possibly being overridden in an update.
It is always best to keep local copies of the originals and your changes just in case you need to do a quick fix after an update.