The goal is to have them isolated from the outside world beyond the Americas, even if the Spanish don't have a hold on Mexico, they'll eventually find their way south to the Incas.
That's cool. I've been preparing a TL with a similar premise, still in the brain-formulation stage. LOT of work and big implications for a PoD like this.
If you're just concerned about keeping Tawantinsuyu alive and pristine-ish, that's why I recommended a failed invasion. See, the Spanish officially never intended to invade Mexico. That was all Cortez and he risked a lot. The original plan was to just scout it out and initiate trading operations and peaceful religious missions. If the illegal invasion fails, the survivors would attempt to retreat and possibly find some way to reach Havana. If they don't, Narvaez is still going to hunt them down and he will discover the truth. Either way Mexico's going to be seen as treacherous hostile territory, with armies capable of vanquishing the Spanish. They'll try to keep away for a while.
This buys enough time for 1) the Incas to re-stabilize after their civil war (assuming Huayna Capac still dies of smallpox) 2) legend to spread about shiny stinky hairy people trying to kill everyone, 3) slight immunity to smallpox and some knowledge in fighting it, even if it is scant and 4) you, the author, to work your magic in making them an even stronger nation. Then when the Spanish do get around to arriving in Tawantinsuyu, which would be much, much later than OTL, the Incas would have that much more of a fighting chance and the Spanish would be restricted to trade missions. If you like, they need not even transfer a great deal of culture and technology, just trading commodities and luxuries. They may indeed try to trade for firearms, but whether or not this gets accepted by the Inca army is another thing. For example, bows were known of in South America at the time, but the Inca army preferred to use slings as their primary ranged weapon because of their simplicity. Like the Zulu, firearms could be seen as inferior due to their long loading time and general inaccuracy. If they do get adopted they may only be seen in use by farmers and other civilian laborers.
As for your original plan trying to take Europe out of the equation, that's something I'm still trying to figure out. You may have more success making the Black Death
less bad than OTL, actually. The plagues introduced a lot of change in Europe. But on another note, Columbus' journey itself was a long shot among long shots and stood a very good chance of not happening it all. The very fact that it did happen can be attributed to a LOT of luck and some swindling, and even as he set out he stood a good chance of not surviving the return trip and based it off of a few educated guesses. The fact of the matter is it's unlikely there would have been someone to substitute for Columbus anywhere near his relative time period, as the consensus was that the Pacific and Atlantic were one and the same, and traveling it and making it out alive would be a mere logistical impossibility. Nobody else would be stupid or desperate enough to believe the Earth was smaller than it actually was, and even if they were they wouldn't have the level of ambition Columbus had in trying to pitch his idea (and on that note, he very nearly gave up completely until Ferdinand managed to change Isabella's mind). By that time, the Portuguese were already ironing out a route to the East Indies via the circumnavigation of Africa, so Europe may wind up doing that.