If the data you were backing up was of extreme importance then I would recommend a seperate server with some type of raid configuration (Raid 1 = mirrored hard drives). This way even if one of the backup drives were to fail you would be able to salvage data from the operational drive. You could then replace the defective drive and the server would rebuild it from the working drive so you would have redundancy. This would be a more reliable solution however it may be a little overkill for what you are trying to back up.
In your case I would throw a second physical hard drive into your machine with scheduled chkdsk's and defrags. You could couple this with an additional back up to the USB media to gain redundancy. This way you can take the usb media with you with peace of mind that an additional copy of the backup is stored on a seperate disk that wouldn't be affected by a corrupt OS etc.
I think the most important aspect for a reliable backup is redundancy. Alot of external USB hard drive manufacturers boast about backups and software but if the drive itself fails then you're in trouble. The possibility of having multiple redundant backups fail at the same time is far less likely therefor the backups itself is more reliable.
