I would stay away from GUIDs as a primary key, especially if it gets defined as the clustered index.  For me there needs to be a good reason for using GUIDs as primary key, such as replication.
I like synthetic keys that are invisible to the application.  I also believe that a natural key as one of the alternate keys is valid.  And if you can identify more than one alternate key that could be beneficial as well.

Don't create single column indexes on every column.
Try not to duplicate indexes.  Apparently there may be times when a duplicate index is a good thing, but I haven't found them useful yet (Jeff, what say you).