Apple Blog has a good article on how to create a multi-layered backup strategy:
http://theappleblog.com/2009/06/05/my-multi-layered-backup-strategy/
Some software worth considering are:
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Time Machine or Superduper! for daily painless backup. this is your first line of defense
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JungleDisk or Mozy for the off-site backup (just in case time machine is corrupted or your house is on fire. This is your reserve backup
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Dropbox or Syncplicity to sync files to other machines on your network (good to have a backup of "critical" files). This is for the worst case
There is also
CrashPlan that is a little expensive but can take care of all these three facets.