Mine runs fine on an old Q6600 with 4G of RAM. I'm not trying to do anything silly, like enabling dedupe, so it's not a problem. I'm running ZFS on Linux, again, not a problem with that amount of RAM despite ZoL having a less than ideal caching situation in the kernel.
I do my backups with Crashplan. Not only do I back up the NAS with Crashplan, but I back up my various PCs and laptops to my NAS, for faster restores should I need it. Crashplan supports peer backup, which works well.
I tuned my recordsize by copying a representative sample of files to different ZFS filesystems with different settings, and comparing du output. The empirical calculation seemed easier.
I've used my NAS for a various things; video / photo archive, VM backing store (serving up zvols as iSCSI endpoints), working space for a variety of side-projects. More than anything else, it gets rid of the idea that storage space is in any way scarce, and removes the requirement to delete things (very often, anyway; I built up several years worth of motorcycle commute headcam videos at one point). My pool wanders between 40 and 70% utilization.