Margaret/Margherita as second wife for François instead of Eleanor make a lot of sense for both sides as that wedding will consent the confirmation of the bethrotal between the Dauphin Francis and Maria of Viseu (who OTL was make impossible when his father married her mother)Karl V MIGHT offer Margherita for François (particularly if he and his siblings have male heirs. So there is no chance of Burgundian Inheritance falling to the distaff line of Margarethe) with the intention of said sons inheriting the late Connetable's estates (like Louise de Savoie did OTL and then passed them to Charles, duc d'Angoulême)
Or to phrase it properly, François might sue for Margherita's hand with this intention and Karl decides that it's an option to stir trouble in the French pot
Il Duchetto is in French hands from the fall of Milan and will stay there for all his life so the groom will be Massimiliano (that unless the wedding was delayed until after the reconquest and fall of Milan who had seen also Massimiliano captured by the French and so the groom will be Francesco II) and yes here Margherita’s son will marry Kristina of DenmarkOtherwise, a marriage between Margherita and whichever Sforza duke of Milan (il Duchetto, Massimiliano or Francesco II) seems interesting. Their son can marry Kristina of Denmark ().
As much as I like the idea of a Neapolitan match, I'm not sure Karl V will go for it. It's in his interests that the Neapolitan Trastamaras go extinct. He hardly needs a side line (think of them as Neapolitan Braganças) which can threaten Spanish rule there. Although a lasting line there could be beneficial since it gives the Habsburgs one less kingdom to worry about the French taking, and a convenient bridal orchard (rather than the constant intermarriage between Madrid/Prague/Vienna).