Is this just for loading backups or are there other things you'd like to do with it? I personally would recommend Configurable USB Loader and a hard drive formatted to FAT32. You would then use games in WBFS format (a scrubbed format) instead of ISO. Although FAT32 allows files up to 4GB in size, I recommend doing a 2GB file split with your games instead of a 4GB file split.
Having a hard drive formatted to FAT32 also allows you to use HBC to load apps right off of the drive. You can keep CFG USB Loader's boot.dol, and others, on the USB drive, instead of needing to update the SD card (or whichever is easier). But note, that if you want to install a hybrid channel or forwarder and you keep the loader's boot.dol on the USB drive, you should install the forwarded from the USB drive as well.
Having a hard drive as FAT32 also allows you to keep your disc-art, cheats (gct, txt), WIPs, and other miscellaneous things on the hard drive, instead of having to create a seperate partition. Just remember to format the drive to FAT32 as a primary and active partition.
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