Does it make sense to place DAG members in different sites when the witness server must stay in one of them? Think to this configuration: two DAG mailbox servers, one into primary site with witness folder on a HUB/CAS server and the second mailbox server in DR site and a very very fast and secure dedicated line between them. All users are into primary site, so all databases would be always active on primary mailbox server, with all passive copies on secondary mailbox server. In the case of failure of primary site, suppose both primary mailbox server and witness go down, will be the secondary mailbox server able to support users?
Does it make sense? Yes
Will the secondary site support the users? Yes.
Will it be automatic failover? No.
Your config won't automatically failover to the secondary mailbox server if both your CAS and mailbox server at your primary site are offline. In your config, your DAG no longer as a node majority for the DAG to be online and the cluster to function.
You would be looking to do a manual site failover.
Honestly, automatic site failover is not advisable. For example: what if your link goes down between them. The failover site will think it should become primary and start becoming active. meanwhile, your primary site will still think it's active and the secodary is offline and queue changes to send. When the link comes back up, you end up having a mess on your hands to clean up.
Microsoft has some pretty decent articles on datacenter failover in Exchange along with the steps to perform a site failover. (http://technet.microsoft.com/en-us/library/dd351049.aspx)
If you do this, please consider using DAC mode (http://technet.microsoft.com/en-us/library/dd979790.aspx)