I agree that this is major issue in BuddyPress – people tend to reply to e-mail notifications instead of going back to the BuddyPress platform and posting a reply there.
As far as I understand the Mail From plugin simply defines one overall sender address. You can enter the admin’s email address here, and he will get all the reply mails. But that’s not what you want – you want the reply beeing posted to the discussion thread in BuddyPress. 37signal’s Basecamp does this nicely. Is there a plugin capable of doing this?