I've found the first thing in backing up a system is considering backup when designing and building it.
My PC had a single 2TB drive. I partitioned my C: drive to be 32GB; my data disk (D:) is about 200GB, and other drives based on function. My M: drive is music, for example. I have an external 2TB eSata disk (B:), also 2TB in size, a networked PC with a 2TB drive (P:), and a 2TB USB drive I keep in a fireproof safe.
The reason for having a 32GB C: drive was specifically for backups; you can image a drive like that in about ten minutes, and write it to any number of 32GB media options; hell, I picked up a 32GB USB 3.0 thumb drive the other day for twelve dollars. This also really helped when I picked up an SSD disk for my C: drive; I just imaged my existing partition to it and I was set. Friends who had 500GB C: drives went through hell trying to figure how to generate a C: drive which was current with all their config data and installed programs, etc.
Every morning at 4am, a cron job kicks off - a TCC script, which does various things on various days. On Tuesdays, it generates an image file of the C: drive, and saves it in a directory on the D: drive. On Wednesday through Monday, the D: drive is incrementally backed up to the network P: drive (which will back up the image of the C: drive to the network), as well as differences on any other data drives. I've found the best command line file copy utility is the Robocopy tool (free download up to XP; built into Win7 and on), and the best Windows based backup is SyncBack. Should my primary PC die, the secondary PC will have all the files from it current to 4am the morning it crashed. It will also have a bootable Macrium image file of the C: drive, which in the worst case scenario would be 8 days old.
I used to automatically close the command window on completion, but I could potentially miss a fault, so I don't do that any more. Every morning, when I turn my monitor on, I see the window showing the status of the successful backup. If I don't, or if it shows a failure, then I can take corrective action immediately.
Of course, there's always the possibility that a fire or somesuch could wipe out both my primary and secondary PCs, which is why I have the fireproof safe. The first weekend of the month, I take the 2TB disk out of the fireproof safe, and run another TCC script, which clears the destination drive, and then images my C:, D:, and other drives to the USB disk. That takes a few unattended hours, and then the drive is tossed back into the safe for another month.
Now, show all of *that* fail, I also have two 2TB encrypted 2.5" drives, on which I make an image of my system monthly. I rotate them, keeping one offsite, and one at home. Should my place burn to the ground, and even the fireproof safe not be saved, I will have an offsite backup that is at worst case 29 days old. Yes, I realize that at any given time, my PC data has no less than five separate backup copies, including one stored offsite. But with the exception of the monthly backup, which takes all of about five minutes to hook up a USB drive and start a shell script in a command window, it's completely automated.