This may be a bit wankish, but hear me out.
If D. Carlos were to marry (either Élisabeth de Valois, if Mary Tudor lives a smidge longer; or Anna of Austria) and have kids, would said kids be able to inherit Portugal when the Cardinal King dies? And if they do, would Felipe II EXCLUDE his (Portuguese) grandkids from his first marriagewith regards to the Spanish succession in favour of a son from a later marriage (i.e. D. Carlos still dies before Felipe II, but leaves underage son(s))? I ask because an exclusion due to underage kids happened with the de la Cerda infantes, and Fernando el Catolico attempted to play the foreign monarch card with Karl V. Plus Felipe II's dislike for his eldest son and I figure it could have legs, no?