If you simply delete the contact, they could potentially sign back up again with the email address if they do want to receive emails. If you unsubscribe them, they'd need to go through some kind of process to get resubbed. If the former employee doesn't even have access to the email address in question, it's probably safe just to delete them.
One other thing to note is that if the employee was granted any level of access to the account (e.g. a verified address or user role), you'll want to make sure to remove that. If they're a verified email address, you can remove them via the My Settings page. If they're a Campaign Creator or Account Manager, you can deactivate their username-password setup to access the account.
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ William A Community & Social Media Support