It's perfectly plausible. Half the Empire was tentatively collaborating with Pizarro's usurpation of Atahualpa. Throw out the idea of 'rebellious oppressed natives' leading the charge akin to the Aztecs. If anything I think the idea gets horribly overhyped. In fact, let's play with labels the way the 'battle' of Cajamarca was. Humor me on this thought experiment. It'd be more appropriate to retroactively label the Empire dead with the death of Huayna Capac and the start of Civil War, and to label Huascar's Inca Empire the Southern Inca, and label Atahualpa the Northern Inca. We could correctly label the capture of Atahualpa and the temporary pseudo-shogunate imposed upon the Andes as the 'Inca Captivity'. And then we all know what the Neo-Inca Empire is.
The Northern and Southern Inca had their final battle days before Pizarro showed up, and the Northern Inca had not marched on the Southern Inca lands directly yet. Remember, the only force opposing the Spanish actively were the Northern Inca. The war was largely fought in their half of the realm. The soldiers that fought were already past their terms of service, and had fought through (some sort of) plague and civil war. Let's skip over the 'it wasn't smallpox at the time of the civil war!' crowd, that's a non-argument(IMO) when the damage caused by war and disease to the Inca, smallpox or not, is apparent.
The point is, two rulers died in quick succession to a mystery disease, a civil war was fought that was a milestone moment in Inca history not only due to it being the first but also the start of an eventual societal collapse, Pizarro's timing was 10/10, and only half the realm was even willing to fight him and it was the more dead half of the realm. The Southern Inca were only willing to fight at the end of the Inca Captivity, and weren't militarily competent enough to siege their own stone fortresses in Cuzco...but credit where it's due, Cuzco's fortifications were crazy. The Inca can build fortresses and then some.
So yes, I think an organized Inca Empire with one man at the helm that hasn't burnt up their war-waging capabilities juuuuust prior to Pizarro's arrival would actually do quite well. I think they'd have hell retaking some of their own fortifications in the face of large resources being put into holding fortified positions with firearms and steel, but it's not impossible.
The only question remaining is do the Inca adapt fast enough or survive long enough to live past Spain's apex, or are the Spanish able to commit enough resources to crack the Inca egg like OTL before their overcommitments ruin them. The answer is, whatever your TL or headcanon demands. Neither is unfeasible.