The best option to achieve to keep Spain in the big powers group is that the economic reforms that were attempted to reach had better results (I´m talkin about Finance or reforms of enlightenment age). Also in this line, we were a great power with the first Bourbons and we were doing great but our alliance with France killed us. We failed to get rid of France.
I don't think that expel the Jews in 1492 could be the worst failure in spanish history. Against the opinion of many people, the Catholic kings didn´t hate that much people of other religions. Its main objective with the expulsion of the Jews and the Inquisition was to create a unified state and that it succeeded. Their reasons at that time were totally and absolutely justifiable. We could have gone better with the Jews in the peninsula but WI we are going worse with them? I only know that this is not what defeat us
Spain would not create an empire that lasted centuries and keep strong by the mere fact that the crown get in the hands of Miguel like Condottiero says (no offense,I love your Trastamara TL and congratulations on this) . The kingdoms would still be really disunited for a few centuries and Portugal would still be able to maintain its rule over their colonies before any nation enemy of Spain. I think that was the last best option to unify the peninsula before Philip and that could be cool and could maintain the unit until today but does not mean anything in the economic field.
About Burgundian Inheritance, yeah, that was other of our rulers failures, but I don´t think that the worst. Yeah, that get us in loads of wars but there has never been an empire that lasted forever and in that time, Spain ever could get enemies, with or whithout Hapsburg personal union. When we allied with them, we need them. The only thing is that Netherland NEVER had to go into the hands of Philip. We ever get excelent trade relations with the Netherlands and we could maintain that after Charles, but we could survive the wars.
Greetings and be fun