Well, I can tell you how I have setup my system. I run VMs, audio and video editing of all sorts and web authoring. What I have learned is that if you are running Virt-Manager for VM’s (Which I highly recommend), you need to have a separate partition for /var, virt-manager stores the VMs in /var/lib.
The home partition, IMHO, should always be on a separate drive. Also, the root directory should be at least 50Gb.
EXAMPLE:
/boot/efi (drive 1, partition 1)
/ (drive 1, partition 2)
/var (drive 1, partition 3)
/home (drive 2, partition 1)
Number one reason to have /home on a separate drive is in case of system corruption. You can reinstall the OS without formating the /home directory and you are back in business.
For backup, I use Timeshift for the system back up and BackInTime for the user directory.
Be sure your backup drives are large enough for backing up your VMs.
As for the file system type, you will have to make an educated guess… I have been running my two NVME drives in EXT4 with no issues for a year. I also understand that Fedora 33 is shipping with BTRFS…