So, lets say Juana the Mad (Ferdinand and Isabella's daughter) is born as, oh, Juan the Mad, and thus, the folding of Spain into the Hapsburg monarchy doesn't happen. Instead, the Hapsburgs go into the 16th century with just the remnants of Burgundy, Austria, and Milan. A couple things I can see:
-With the Low Countries (which was, from my understanding, the wealthiest area of the HRE), plus Austria, the Hapsburgs will be in a much stronger position in the HRE. Is it possible that they might be able to unite it into something more resembling the French kingdom at some point?
-Assuming Martin Luther and the Reformation happen ITTL, how might the Austrian Emperor handle it differently, considering he won't be in Spain half the time?
-The Hapsburg's Dutch possessions are going to be richer than their Austrian ones (doubly so if they don't get Bohemia). Is it possible that the Empire might become Dutch-speaking instead of German-speaking? Or some new half-German, half-Dutch interlingua evolve and become standard throughout the HRE?
-How might Spain develop? Without Burgundy, I expect they'll be somewhat isolated from the rest of Europe, able to focus more on their navy and their possessions in the New World. Might the OTL post-1600 decline of Spain be softened/averted?