Apart from the Drobo and the HP mediasmart are there any other suggestions?
I'm using an old(ish) machine, packed with drives (7TB), running an old freenas nightly build using zfs - Current uptime is 327 days and network throughput is much higher than any of the commercial offerings I've tried. AFP etc is well supported.
The project has been forked (and rewritten) by the 'main' dev to a linux based system, while the original freebsd based code is being rewritten by ixsystems to provide a freebsd 8 (and therefore current zfs) implementation - Works fantastically at the moment, and I'm sure will be even better in the near future.
Unraid is a similar alternative, but runs a proprietary system - I don't have much experience with it (not hugely interested). Requires a parity drive and allows for easier additions of different sized hard disks.
Pretty much any machine (consider recycling your old machine/parts instead of buying a new device?) running any OS could be set up to be good file server/backup device/any other services you might want. Not quite an out of the box solution as freenas/unraid/nexenta/etcetc or especially the specific use commercial offerings - On the other hand, you'll likely save money, have a more adaptable system (not locked in to specific uses/services or disk limited by hardware), not have so many problems if/when something does go wrong, and have a higher network throughput.
Time machine backups are easy to change to any network based storage system if that's a priority of yours (Personally I much prefer using rsync).
I don't use itunes. Since itunes >= 7 when apple changed the daap protocol without documentation, I'm unsure how well any of the itunes streaming/services work - if it's a number 1 priority, you might have to stick with an OS/system that simply runs an itunes client/server or has it's own (and working) alternative.