I am laying piers with 12 x 16" block 48" deep in the ground to support a 1 story shelter that will be on posts about 4' off the ground. Does it make a difference if I use sand mix or mortar mix to lay the block.

The mortar selection is certainly critical, for strength and durability.
The highway/bridge agency I worked for followed the research of the Portland Cement Assn. and ASTM for design of concrete and mortar. The following reference from the International Masonry Institute looks reliable to me. One factor is always certain with cement based mixtures: Don't use one ounce more water than is necessary to complete the chemical reaction. More water always means less strength.
http://academic.csuohio.edu/duffy_s/593_02c.pdf

And if I were building a critical structure using mortar I would be looking into an air entrainment admixture (such as the one linked below), having seen the effects on durability of concrete with and without air entrainment, especially with regard to the impact of freeze-thaw cycles. The air will reduce the strength slightly but be well worth it for durability.
www.ae.graceconstruction.com/concrete/download/MORTAIR_1.pdf

If a permit is required, also refer to the specifications which pertain to your project.

Mortar mix is designed for bonding block and brick. It has a "stickyness "factor. Sand mix is mostly used for overcoating or topping and is harder to use in setting block. In your case, probably not much difference but mortar mix is preferred.