Here’s a short outline of my current backup setup on Qubes OS.
For user data, I use BorgBackup with encryption and deduplication enabled. The same data is backed up to three different targets: an internal disk, an external disk, and a remote server. Deduplication keeps the storage overhead reasonable, while encryption is handled end-to-end by Borg.
Separately from that, I use the built-in Qubes Backup for system-level backups (VMs, templates, and configuration). These system backups go to an internal disk and an external disk.
I deliberately keep user data backups and system backups separate. Borg gives me efficient, flexible, file-level backups for data, while Qubes Backup gives me a clean way to restore the whole system state if needed.