This is from my view as a user of Backup Exec for years.
In a file server, some users will not close file that they are editing before leaving the office. Especially Outlook PST file.
Without AOFO agent, pst files will be skipped because they are still opening.
I suggest to use AOFO unless you kick out user connections during backup windows.
Above is to protect user files.
For system files, the system is keep running and keep opening files all the time. If you want to protect the system as well, use AOFO.
I purchase AOFO for all installation.