My main use case for me is iSCSI LUNS for VMWare; iSCSI LUNS for Hyper-V, SMB with a 5TB VHDx file, general file sharing.
To that, what you're asking is if FreeNAS/TrueNAS can act as a SAN. Yes.
The file system you put on the LUNs is up to the system connecting to it...VMFS is a cluster-aware file system, as is NTFS when used as a Clustered-Shared-Volume (CSV). The attaching operating system has to be cluster-aware, as would it's file system, as would the operating system likely need to be aware of others that are clustered with access to the LUN. IE, don't run two clusters with the same LUN(s)...though, VMWare seems to be a good bit more tolerant to that kind of thing w/ VMFS.