DB Design - 1 column for each dataset OR dataset_name AND dataset_value?
Upon realization that I had unwittingly reinvented a modified EAV model with Option #1 and would likely be headed into a world of hurt with this option, I decided to go with Option #2.  

Option #2 should preserve many of the benefits of RDBMS and I think MySQL/InnoDB can support the row sizes I currently expect.  While I will have a quantity of NULL entries that some might find disagreeable, I expect the DB will perform queries quickly, which is my main concern.

At some future point, should I hit constraints/performance issues, I may consider a NoSQL option as it appears the data I am working with doesn't necessarily correspond so well to RDBMS.