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What if the Ferdinand I were given the Habsburg lands in German, which would include the Netherlands, Luxembourg, and Franche Comte? Let's say that because the Hungarians win at Mohacs and their King Louis II survives to have children the Habsburgs don't inherit Hungary or Bohemia by Charles V's death, so in order to strengthen Ferdinand's position in the HRE Charles passes the above lands on to his brother. The Italian lands pass on to Spain as OTL.
Obviously Protestantism is going to be a major issue when it spreads widely throughout the HRE, but without the Turks (at least before 1560) besieging Vienna, Habsburg focus will remain on the HRE and struggle with France.