Regarding cross-pollination with respect to viruses such as Cryptolocker, that potential risk exists with any file or media server arrangement that can be accessed by multiple clients. Cryptolocker scrambles a shared network drive that is accessible to an infected PC, just like any file on that PC.
The way to reduce that risk is to limit access rights to "read only" by the client PCs, and to allow only one PC to update the media files. That way, your children's or wife's PCs cannot zap the music files or photos that you have carefully archived.
Of course, the directory where you store finance records should not even be permitted access by just any client on the network.
About WHS using "Single Instance Storage" to backup common Windows system files from client PCs, it does not cross-link files just because they have the same name. The files must compare bit-by-bit before they are stored as a single file. So, WHS will not spread a virus-infected file from one PC to another. And these backup files are only accessible to WHS and not any client PC. And WHS itself needs anti-virus protection.
On top of that, I still maintain duplicate backups on a stand-alone 1TB media server, and yet my main desktop PC with 2TB storage. The WHS PC, the stand-alone media server, and the big PC are linked with wired 1Gb Ethernet for transfer speed. And I still have another older 1TB Buffalo server with built-in RAID capability.
But I still have to remember to put a backup on my 1TB USB drive and take it out of the house for fire protection. Put it in the motorhome, perhaps?