ReadyNas516 RAID

You can't change to that configuration without destroying and re-building the array.  But I'm not sure why you would want to -- you end up with the same usable space and less redundancy.

With 1 x 2TB and 2 x 4TB in RAID, you have one 2TB x 3 layer and one 2TB x 2 layer.  One of the 2TB's in each layer is redundancy.  So, you have 6TB, or 5.44TiB (the measure te NAS uses).  With one 4TB x 2 volume plus a separate 2TB volume, you use one 4TB drive as redundancy for the other 4TB and the 2TB has no redundancy.  But you still have 4TB + 2TB = 6TB of usable space.

If you replace the 2TB with another 4TB, it'll grow by 2TB.  You'll have two 2TB x 3 layers, still with 2TB of each layer as redundancy.   But if you add the extra 4TB to an empty slot, it will grow by 4TB.  You'll have one 2TB x 4 layer and one 2TB x 3 layer, still with 2TB of each layer as redundancy.  Unless you have a drive going bad, it is generally more effficient to add drives till you have no empty ones, then replace starting with the smallest.

Use this Netgear RAID calculator to do your "what if's".  Note, however, that the calculator does not address expansion limitations.  It doesn't keep track of the order in which you add them.  While 1TB + 2TB + 2 x 4TB would work if inserted in that order, you cannot add a 1TB to your array at this point and have it expand.