Is it ok to use "relayhost" in Postfix /etc/postfix/main.cf? Is it safe to change main.cf? Will Plesk, now or in future, change the settings?
What would be the prefered way to configure an outgoing mail relay in Plesk?
Yes, it can be configured in /etc/postfix/main.cf, but it is also possible that within future Plesk updates or upgrades, such configuration is reverted back to the original state, loosing such custom settings. Moreover, a Plesk migration doesn't carry those settings to the new server.
In Plesk it's not possible to configure outgoing mail relay, so please suggest (or vote) such functionality in our Plesk Uservoice channel. Most voted features will have high chances of being included in future Plesk releases.