Is it possible to target a specific instance in a clustered environment with group policy?
Community Wiki answer generated from a comment on the question by Steve Mangiameli

It is, but you'll need to be a little creative.  Remember, you will be setting two different permissions sets - OS and SQL Server.  Hopefully, each instance has install and DBs set in different directories, for each instance.  OS level permissions should be directed for the disks/directories for that instance.

SQL server permissions are relatively simple at that point.