Best way backuping WS2008 to off site

Get a second 312.

Backup using 3rd party software to local 312 then use ReadyNAS Replicate to backup to off-site 312.

Using ReadyDrop too maybe ?
Otherwise there are classic solutions without ready cloud like bittorent sync or rsync over SSH that won't copy the whole files. I think Crashplan can also do it but would require some work to get on the NAS.
The problem I see with replicate is that you need to use either Rsync, bittorent sync or crashplan (or anything like that) to avoid copying the whole DB each time you backup, even if this is local (between the server and the NAS) and fast (gigabit).

Does the database server have any mechanism for WAN replication built in? Usually, that would be the best choice. (Some type of journal-based replication is usually used.)

If it doesn't have any type of built in mechanism, and doesn't keep a journal you can replicate, then you're going to have a very hard time finding ANY real-time replication solution that could ensure a non-corrupted database copy.

Knowing a bit more about the source database would be helpful. Some databases could probably be coaxed into directly replicating to a WAN server. For example, I believe modern mysql supports WAN replication, and a mysql server could also be installed on a readynas device...

With Windows server I assume DB is SQL server. Most of other DB prefer linux.
Anyway replication is great but can't be done on the 312 unless this is one of the linux compatible DB.