It's MAJOR drawback for any use except backup, is the excrusiatingly slow transfer speed of USB2.
Not entirely true, it depends on the device. A properly implemented USB2 interface - on both sides of the cord - is on par with FW400. For data transfer, realtime transfer speeds can stutter because of OS interrupts but that's only important if you're working with something audio or video. For backup, it's fine.
Firewire 800 is certainly better for striped RAID work drive setups, but eSATA and Fiber Channel is even better, at least if you're running faster than 7K hard drives.
But all that's out of my price range, so I just back up to duplicate external drives. One stays at the studio and the other goes home with me. When the drives gets full I simply print a folder list, put them away, and buy two more.
Anything recent or other things I want quick access to stays on my work drive, but the bulk of my archive resides on the shelf. A bit inconvenient if I want something from it, but very large storage arrays where my life's digital work is always available, are far too expensive for me right now.
The duplicated external drive solution is inexpensive, safe and effective, and plenty fast enough for backup and archiving. The only time I'm vulnerable is if my work drives suddenly fails before I've backed it up, but then RAID setups have their own share of drawbacks, like if you accidentally delete a file it also gets deleted on it's mirror.
FWIW, I always bring an external drive with me on a location shoot if there's any chance that I'll exceed the capacity of my flash cards. Of course I backup to my laptop every time a card is full, but I don't erase the CF card until it's data is in two other places.