Welcome to Tom's Hardware, @bkeith!
It really depends on which HDD you are planning to use as a boot drive and which one as a slave drive.
The slave drive should be configured as a secondary storage for your massive data, whereas the booting one will need to contain the operating system (where Windows is installed) and any other programs you wish to have on there.
It also depends on the drives themselves. Do you have an SSD among those drives? What are the specifications of the hard drives overall? All these things matter.
It's preferable to use the fastest HDD you have for the operating system in order for it to boot faster.
Keep me posted with the details in order to be more helpful.
Cheers,
SuperSoph_WD