There's no "right" solution, each person needs to trade off risk vs cost vs convenience. I'm an experienced pessimist (equipment has and will continue to fail) and inherently lazy

. So here's what I do as an example (Windows, but Mac can do the same). This covers what I consider my important files (images, music, receipts, email etc). I deliberately organise my files so I know what really matters (about 120GB so far) and what is the accumulated detritous of a life time of hording digital stuff.
1. Backup to an internal drive dedicated to backups using ShadowProtect on a 2 hour cycle (TimeMachine would do similarly on a Mac). I've tried many Windows backup solutions, ShadowProtect is fast and robust, built for enterprise use really.
2. Backup regularly to external drives using SyncBackup (on a Mac try SuperDuper); these drives are only powered on and plugged in for backups. I like copy/sync software that has the option to actually compare file contents, not just check date and file sizes. Once in a while a copy operation will (probably silently) result in a corrupt copy. Fact of life if you move enough bytes around (strange nobody mentions this in the brochures)>
3. Use both Carbonite and Mozy for online backup.
Personal circumstances make a traditional offsite backup with external drive tricky. On the other hand, I also apply my usual level of pessimism about the online backup companies. By going for two (which frankly cost peanuts compared with the data value) I've mitigated the risk: different companies, different backup s/w, different server locations.
Sure it takes a while to upload at first, but every file uploaded is an instant mitigation of risk. Once you have it all "up there" I find the daily load quite manageable. I'm also mitigating my laziness - those files will be offsite within 24 hours. No way I can match that with offsite external drives.
Sure it would take days to download again. Then again, I only plan on needing to do that if my house-office burns down. Under those circumstances, I'll wait a while. If your needs are such that you can't wait, then by all means use offsite drives - they just don't suit me.
cheers, martin