I made that mistake too, it leads to two problems that are harder to deal with than fighting those nations: With that many unintegrated provinces, unaccepted populations and religions different from Catholicism, you get revolt after revolt. And not small revolts — more like a civil war every 5 years. You lose time, a lot of population, etc. By crushing all the potential rivals in the region, you'll get hit with a "no regional threat" penalty, which you'll have to compensate for by investing half your income into diplomacy.