Nick,
The CIFS object cache in WAAS (either in 4.0 or 4.1) is by server name or IP address. So if you preposition a dfs share, it could be from the leaf node closest to your core WAE, which may not be the one closest to your users at the edge. You can affect this by naming the WAE location where you want to preposition from (http://www.cisco.com/en/US/docs/app_ntwk_services/waas/waas/v411/configuration/guide/filesvr.html#wp1043516). The CIFS acceleration is designed to be transparent to the end users and to use autodiscovery to accelerate remote servers, including DFS servers. You should not have to join the WAEs to the domain, it should be transparent to both them and the DFS servers.
Are the users going from a local server to a remote server and their responses are worse? Or they had a remote file server and now it's worse?
Can you tell if the users traffic is being accelerated by the CIFS adapters? Look in the connections listings to see if the CIFS adapter is identified in them.
Hope that gives you some places to start looking,
Dan