Disease was still very much the deciding factor. The europeans had an advantage in technology, but not a staggering one. Cortez's forces were successfully defeated by the Aztecs on more than one occasion, and it was only after disease wiped out a large portion of Tenochtitlan's population and a protracted siege that Cortez and his allies could wear down their defenses enough to seize the city. When Pizarro entered Peru, the area had already been severely depopulated by disease and civil war, the civil war itself being kicked off by the death of both the Emperor and his heir dying of small pox. He convinced the winner of that civil war to visit him unarmed and then captured him and masscred his retinue, and used his hostage to get the Inca generals to stand down. When the Incas eventually rebelled, they too were successful in the field against the spanish - Manco Inca managed to wipe out 4 relief columns sent to break his Siege of Cuzco. Guerilla tactics were common but Manco also defeated the Spanish in open battles, such as the Battle of Ollantaytambo. While Manco was ultimately unsuccessful in seizing control of Cuzco, the Spanish likewise were unable to defeat him, and his Neo-Inca state survived for decades.
