I have created partitions large enough for everything on my laptop’s hard drive on each of the external hard drives. Then I periodically clone the laptop to the external disks using SuperDuper!’s Smart Update feature, which only copies changes. It usually takes 30 minutes, where I do something else. I then alternate between the two drives, so that if something fails during backup (which is likely), I’ll still have a working copy.
The major benefit of this system is that I can plug the external drive into my Mac Mini (over FireWire, not USB), and boot from it, and immediately continue working from exactly where I was while my computer is away for repairs. Not worth doing for a hard drive replacement, but for something more serious, it’s an option.