Deciding on datastores for your new VMware ESXi 8.0 server with 20TB RAID 5 storage involves balancing performance, management ease, and availability. If your VMs, like a domain controller, application server, and file server, have varying I/O demands, consider separate datastores to prevent one VM from affecting another's performance. Separate datastores also simplify management and enhance fault tolerance by isolating VMs. However, if your VMs have similar needs and simplicity is key, a single datastore might suffice, streamlining operations. Choose based on your VMs' requirements and your preference for simplicity versus granularity in management.