Ideally I want to plonk in 4 identical drives and have 2 drives as one volume which is mirroring the other volume of two drives, so I get 6TB of usable space.
Is this possible, or even a smart thing to do, or can I get better protection from failure with a different setup?
The default X-RAID (like RAID-5) would give you about 8TB of space.
There are multiple raid options open to you: RAID 1, 5, 6, 10 etc. You may wish to read up on these.
Whatever RAID you use if you store important data primarily on the ReadyNAS you should backup that data regularly, preferably keeping a copy off-site at all times.
