Here are a few best practices recommended from years of experience and much customer feedback.
Multiple Backup Sets
This practice is more relevant to servers with larger data sets (e.g. over 50 GB) but can be used for all sizes. Creating multiple backup sets to "split" up your data in to different sets gives you much more flexibility. For instance, you may create one backup set for "C:\Users", a second set for you 3rd party application files, and maybe a 3rd backup set for all of your "User Shares". This will allow you to create relevant "Filters" and "Schedules" for each set of files.
Local Copy Backups
When using our "Local Copy" feature that allows you to keep a backup of your data on a USB or network drive, as well as off-site. It is recommended that if you want a backup set to be both for "Local Copy" and for "Offsite" that you combine them into one backup set. This is so you minimize the time needed for backup jobs since the data compression and encryption only happens once.
Temporary Cache Directory
If you are able, it is a good idea to change the "Temporary Directory for storing backup files" to a destination other than the "C:\" drive. This setting is found in the "Options" section of the backup client. Be sure this drive has enough space to accommodate the temp files. This is not relevant for "File Only" backup jobs, but especially relevant for SQL and Exchange backups.
File and Folder Filters
File and Folder filters are very powerful not only to save storage space by not backing up irrelevant files, but also to simplify restores when the time comes. Here are some examples of how Filters can be used. How can I use "Backup Filters" in my jobs to keep out unwanted data?