Depends on the amount of data you are writing and the DWPD of an SSD. Also, take into the account parity if you're doing RAID: https://support.liveoptics.com/hc/en-us/articles/360000498588-Average-Daily-Writes

Well, R720 is quite old. I would look into R730/R630 options. Or ideally, use some hardware that you already have. An old laptop with Proxmox might very well be a start.

I would honestly just go with two separate mirrors unless you need performance (of course if all drives are CMR and on the same RPM level). With MDRAID or ZFS.

What's gonna be the workload? I mean, there is caching of course but you could put some most performance-demanding VMs on NVMe drives in ZFS mirror, some slower VMs on 2x4TB drives in mirror and the rest (file, media server on 8x8TB drives in RAIDZ2).

Sorry if I missed that but what's gonna be the OS? I mean, on Linux, you can just use Linux Software RAID which is old but gold and will have better performance than ZFS. Otherwise, there are tri-mode NVMe/SAS/SATA controllers.

Honestly, I wouldn't go with Storage Spaces. Just unreliable. If you're willing to take the risks, forget about GUI for a proper performance: https://storagespaceswarstories.com/storage-spaces-and-slow-parity-performance/ Also, no to RSTe. I would personally go with a hardware RAID controller on Windows.

Are they add just as any other drives to the RAID controller or hot spares as mentioned? Also, are they the same drives as others?

I think that falls under the homedatacenter category:) Looks very decent though!

If you're looking to use it to run some VMs and containers - Proxmox. If you're going to use it as a NAS - TrueNAS.

Is boot drive selected in the boot order? Probably yes, but just to check. You can also try using Starwinds free converter: https://www.starwindsoftware.com/starwind-v2v-converter to convert the disks to raw or qcow2.

TrueNAS needs direct access to drives to ensure proper corruption detection and repair which is not possible with a hardware RAID controller. But if you're on ESXi, you could just deploy a Linux VM with Plex on a hardware RAID datastore.

And another vote for Proxmox just in case. For containers, just spin up another Linux VM.