As a matter of fact, Spain did effecitvely annex the kingdoms of Naples and Sicily between the conquest operation of 1735 and the Treaty ov Vienna of 1738, with southern Italy being trated as a kingdom within a Personal Union with Spain. During the Treaty of Vienna, Charles, Bourbon Duke of Parma and Piacenza, renounced to his ducal title in favour of the Hasburgs, as well as renouncing to any claims on the Tuscan throne, both of which were given to the Hasburgs. In the previous treaty of 1725 (also in Vienna), it was stipulated that the thrones of Parma, Piacenza, and Tuscany would be given to the sons of the Queen of Spain should the male line for their thrones be vacant; while Philip V of Spain renounced the right for the Kingdom of Sicily (don't know about Naples) to revert to the Spanish (meaning even if it was conquered, it would not be governed by the same monarch as Spain).
In a nutshell, it is pretty complex, Isabel Farnese wanted to have more of his sons in Italian thrones, while Philip V was not that interested in acquiring back Southern Italy, that being more of a trait of Spanish PMs such as Ripperdá or Alberoni. I don't think preventing Charles being granted a throne he could exchange for Naples and Sicily (for example during an alternate 1731 Parma Crisis) would work, as he would still be given southern Italy while delinking it from the main Spanish line. I feel the best way for this to occur would be changing Isabel Farnese, either having her have less kids, for them to die at young age, or for her not to be so focused on giving all of them a throne, then maybe we could have Spain take back Southern Italy durng the middle of the 18th Century, albeit that would change pretty much everything regarding the Spanish succession from the 1710's onward.