Hi - we have 15 totally different business units in our global instance. Now some of them do work together or there is a shared services like Studio Rx where everyone goes to, but otherwise they are separate entities. I highly recommend using Groups to do the separating. Because of our org structure, company didn't work as people might report into someone in a different business unit as you move up the scale and Workfront doesn't allow that.
Groups gives you the ability to have group admins (which kind of suck now but I know product is working on it) as well as gives the ability for custom statuses, schedules, and custom forms (since those are tied to groups).
It isn't 100% isolated because we have one team that uses agile so we had to add a task status called Not Needed/Cancelled to be system-wide for them to do that, (which we have a governance council for). The groups also share job roles, companies (which are clients for us), and they do see the whole list of team names in drop down. But really, it is pretty isolated. We've been doing it for 6 years and haven't had any that have caused people to get their own instance.
