you can manage both domain and workgroup environments trough ePO.
Within a workgroup it can be a bit more challenging to install the McAfee Agent on all the clients.
But as soon as the machine is managed by ePO, you should not have any problems with it.
Once the agent is deployed you won't notice much of a difference.
As mentioned, agent deployment my be a little different, as you won't be able to use some of the built-in functions to assist (AD synch for example).
Notes on agent deployment in most scenarios is covered in the user guides, readme files and the McAfee Knowledge base.