I personally think a world conquest should be possible within the EU4 timeframe, but there was no nation in history big and desperate enough to attempt it.
I mean, United Kingdom, Russia, Mongols, Ottomans, Spain, Roman Empire got really large, but nowhere near. The sheer cost and discipline required to run such a ginormous administration for such a long time would be prohibitively expensive and not just in money but in number of required like-minded people with the right skillset.
I don't actually think rebellions would be that much of a problem for a religiously and culturally tolerant empire, at least for a few decades, perhaps even centuries. After all, all large nations like China or France started out fragmented yet they keep their integrity for hundreds of years.
After a certain size, the "one faith/race/etc." approach stops being beneficial to growth of the empire, as history proves, but EU4 has the right tools to forge a nation capable of it.
The only thing I'd like to see is actually easier conquests if you tick all the proper boxes. Considering how really opressive most regimes were at the time, I don't think populations (and nobles) would mind absorption into a much bigger, more tolerant and economically powerful empire as much as they pretend to in EU4.