Only if you do not disinherit Enrique, I think. (or lack the required DLC for that...)
It all starts with Juan II, with attributes 1-1-2. There is no money for advisors. Many cheap provinces, some of which are constantly pillaged by Tunisia, Morocco and others. This leads to devastation and the impossibility of prosperity.
The Renaissance is taking a very long time. The first mission to conquer Andalusia is possible, but requires mana, and besides, it cannot be converted. Conversion through events is possible, but is associated with a loss of stability. Stability recover requires mana. If you do not restore, then disaster begins.
There is a strong tool like Orders, but there is absolutely not enough mana. Gold mine gives income, but increases inflation, which has no mana to reduce.
Mana is needed for technology and ideas, and quickly. If you are late, then everything will be bad. It is necessary to quickly begin colonization, otherwise the Portuguese will interfere very much. They already interfere, because they have a bunch of bonuses that allow them to build colonies 2 times faster. AI usually fails. Which leads to completely wild results, like French Brazil or the all-English Caribbean. If the second is still understandable, then the first is beyond reason.
I'm not saying it's impossible, but extremely tedious. Any accidental spending of mana can result in failure. That is what is most stressful. Especially after Italy, where I didn't know what to do with it.