These days, I do full-disk-image backups to an external USB drive regularly. It seems to be the most practical way to back up. USB keys don't have enough space for backups. I have two drives on the PC with 1 TB total between them, of which only a tiny fraction is in use. I take compressed backups to the external drive with Acronis TrueImage, and each backup is about 31 GB in size (both disks combined). It is possible to completely restore a drive from a backup in about 15 minutes.
I also have multiple copies of key backups on different external drives, and multiple generations of backups.
Even so, a few years ago I lost 1200 film scans when I had to replace a drive on another machine for which I didn't have a backup (at the time I was backing up to tape and backing up that volume of data to tape was problematic enough that I didn't do it very often). I still have the original slides and negatives (which was one reason why I was casual about backups), but scanning them again would take a long time and I haven't bothered.