I have played with the Inca a couple of times and I can say it is fairly easy to become friend with Isabella. In fact, she is one of the few civs that never declared war on me. Other civs, mainly the non christian one and most of the time Asian civs, were more aggresive with me, but they only sent caravels and sometimes empty galleons against me to plunder my fishing boats.
I believe one the main reason why the Incas are so well protected against land invasion is that there is no direct way to their cities. The northern breach, which allows Incas units to leave their lands through one single land tyle, is covered with jungle and since jungle under the cultural influence of a civ cannot be crossed by its ennemies, no ennemy units can cross there. To the south lies only mountains which are uncrossable. Essentialy, you can only arrrive by boats. And on the wrong side for the Europeans.
Consequently, I don't believe that spawning conquistadors in Spanish colonies will help as they will only be able to conquer incan cities outside of their original lands. The 6 or 7 seven cities in that second category are out of reach even for the biggest military force roaming South America. A solution might be to remove either the jungle tyles to the north, enough to allow a landing party coming from the Carrabean to attack the Inca homeland, or a mountain tyle to the south, making it more likely that conquistadors (if this becomes their new UP) will go toward that breach.
Of course, if there are any ways to make the AI more effective at naval invasion, this is the way to go. Otherwise, I'll continue to keep 2-3 archers (not even longbowmen) in my homeland cities as I know they are safe from arm.
On a side note, I have never waged a real war in the modern world with the Inca, so I do not know if the AI is better with his naval landings with the new technologies.