With the Turks lurking near (Sigismund's main problem), our Charles V wouldn't have neither time neither the resources to make an Italian adventure.
That said, in a Varna Crusade analogue, the Luxemburgs would have more money and troops against the Ottomans, as well a stronger leadership (assuming smooth succession there wouldn't be the retracting of Hungarian royal power that happened after Sigismund's death).
True, but there's always a later point, when Giovanna II dies, that even if she nominates the Aragonese/Angevin claimant to her throne, the house of Luxemburg can say "hold up! We've got a better (marginally) claim to Naples than you! We'll fight you for it if we have to!" but if Charles V is savvy, he'll nominate a second son for the Neapolitan inheritance, the same way his ancestor nominated one son for the Hungarian-Polish inheritance and another for Naples.
I mean, Milan changed hands from the Visconti to the Sforza in the 1440s, yet the French only started pushing their agenda there with Louis XII. Now I know you're gonna say, but Louis was descended, whereas the previous kings were not (and they were kinda busy with a small scuffle going on with England called the 100 Years War), the fact of the matter remains, just because the Luxemburgs let it slide when Ladislao/Giovanna II dies, doesn't mean that they've forgotten about it, technically, it can be dusted off at a later point when they have the resources to warrant intervention. But it's going to be a case of "uneasy lies the head" in the event of whichever king - knowing that they are only
chosen king, whilst the Luxemburg and the Polish royal family (if Elizbieta Bonifacia survives), have a better claim. Simplest solution might be a double marriage between the house of Luxemburg and whichever royal house gets Naples, or even play both ends (Trastamara/Angevin) against the middle (Luxemburg).