Email is easy if you are already using cloud based email like iCloud or GMail etc. Files are more difficult but there are solutions out there to keep folders in sync. If you are just using Apple programs then iCloud is supposed to support syncing but I haven't used it so I'll let others comment on that.
As far as keeping apps and doc's on a separate drive...you could but it would be better to keep the app's local and just store some files on the external if need be. For a lot of us the files are fairly small...its things like video and iTunes or iPhoto that tend to gobble up drive space.
His: 13" MacBook Pro 2.3GHz i5, 16 GB Ram, dual 1TB drives in RAID 0 & iPhone5
Hers: 13" MacBook Pro 2.3GHz i5, 8GB Ram & iPhone5
Family: iMac 20", iPad2, AppleTV3, Airport Extreme & Express