Our history that lead to disabling fast cloning and no align data file blocks:
The backup server has its OS on a SSD and repository on a Storage Spaces RAID10 consisting of 24 4TB 7k2 SAS3 disks.
It is connected via 10Gb Ethernet and hast 128GB RAM.
The repository disk was formatted with ReFS and 4K blocks in December 2016 (when 4K blocks were still recommended). Data integrity is turned on.
Full backups are around 7TB, incremental backups around 330GB.
I configured weekly synthetic full backups and daily incremental (7 generations kept).
On the same disk is a repository for copies (monthly full, 28 days incremental).
The jobs were configured so we have a weekly full to export to USB disks and still keep a longer range of backups without too much disk space usage.
The first weekly backup took only 2.5h (compared to 2h for an incremental), so fast cloning seemed really cool.
During the next 1.5 months, the synthetic full backups took longer and longer. The last weekly synthetic ran for more than 14h and the server got real problems, login was no longer possible and it had to be hard reset. Exporting a full backup to 2 USB3 disks also got slow, so the bottleneck was with the backup server instead of the USB disks.
It seems the disk got badly fragmented with time (certainly the data, probably the meta-data too).
I then reformatted the repository volume with ReFS and 64K blocks (too keep the number of blocks down) and switched back to weekly full backups. The copies use active copy from source instead of forever incremental.
So now we have sequential IO for backups. Since we no longer use fast cloning, I wanted to disable block alignment to save the 10% space.