To be descended from heretics was itself a cause for suspicion of heresy, so New Christians (descendants of converted Jews) were an obvious and easy target. New Christians tended to be in commerce or the professions, the importance of which was not understood in a mercantilist economy. Targeting them was probably popular with ordinary people, who could feel superior to the ‘other’, while appearing to support Church doctrine and making a little money for the Monarchy. I sense there was also a political element, especially when Portugal broke away from Spain. The Portuguese identity of the victims was stressed.
I plan to expand these thoughts on my Sephardic Genealogy website.