I've used the NT File System for the last decade. I use two USB powered drives with my Boxee Box when I take it to my girlfriends. It has zero difficulty playing back my BD ISOs from those drives. It can handle even higher bitrate files when I use a USB drive than from a network drive.
But even from a Network connection BD ISOs are fine since it easily handles network bitrates higher than any BD is capable of.
Boxee Box 1, 2 & 3(Boxee+ v1.4.6), PCs(v184.108.40.20696) Boxee TV(v220.127.116.1181)
Server 1: HP MSS WHS (56TB) (NFS/SMB)
Server 2: unRAID1 (32TB) (NFS/SMB)
Server 3: unRAID2 (29TB) (SMB)
Server 4: TiVo Desktop (6TB RAID 5) (SMB)
NAS 1: Intel SS4200-E (4TB RAID 5) (NFS/SMB)
NAS 2: Dlink DNS-321 (1TB RAID 1) (SMB)