With that many drives, you should also be thinking about controller throughput. With a (relatively) inexpensive PCE 1.1 x4 or x8 controller, I wouldn't put more than about 16 drives on it; even less if your access patterns are mostly sequential.
If you're interested in a concrete recommendation, here you go:
Controller A (PCIe 1.1 x4 or x8):
10 drives in RAID 6 (8 data and 2 parity)
8KB strip size (64KB stripe) -- or maybe twice that if you mostly work with larger files.
Partition as two volumes: Drive C, first 25% of the volume. Install and run Windows from there, along with your applications. Drive E, the remaining 75%, use mostly for backup and infrequently accessed files.
Controller B (PCIe 1.1 x4 or x8):
10 drives in RAID 6 (8 data and 2 parity)
Partition as above, into two volumes, the first 25% (fast) and the remaining 75% (slower). Move your files to the volume that matches their usage / speed requirement.