While it seems very possible to butterfly away a few Spanish losses, thus reducing the tax burden on the Spanish Empire...
The problem is, actual taxes sufficient to defend the far-flung parts (Netherlands, Italy, Portugal) requires local legitimacy, which the Spanish never managed to maintain in the non-Castillian regions (and, arguably, managed with a lot of trouble in Aragon). Without that, it takes lucky strikes on the level of Mexican and Peruvian gold to even begin to defend the country.
However, and this may sound controversial: perhaps not getting the Burgundian inheritance (by not allying Austria, in the process) would be better for just a bigger Empire. It means the Italian front becomes a less acute issue too, I wager (with the Pope providing a natural block for overly ambitious expansion of Naples/Sicily).
As a result, Spain is mostly defending regions that pay taxes. Eventually, butterflies be damned, Spain inherits Portugal, and is in a decent position to use its wealth on fighting Portuguese rebels rather than wasting its resources on Italian and Dutch wars. Eventually Portugal will be integrated as much as Aragon is, so mostly okay but with significant divides. This adds Brazil and a smattering of tradeposts to the Empire, far larger than the Burgundian lands even if possibly poorer.
Now, eventually this Spain will probably still be eclipsed by France, England, and whatever shows up from Burgundy - but it seems more likely to result in dependency than conquest, allowing the Empire to remain huge.