There are a number of reasons for this. A unified Europe would have been very difficult to achieve given the fact that Europe has many national groups who are hard to unite even today. This would have been even harder in this time before easy long-distance communication.
But the most important thing that was specific to the time of Charles V was the Reformation. It was during Charles’s life that Martin Luther started the Reformation. This event caused major splits in Europe. It split countries that went Protestant from those that stayed Catholic. This made unification even harder than it would otherwise have been.