The fall of tenochtitlán in 1521 was significant because

It was a major step in the big cultural ( and ethnic and religious) shift in the Americas: From the Indigenous cultures to European ones. The Aztecs and the Incas were the only empires strong enought to stand a chance against the conquerors, and when  they failed, the whole continent basically "stood open" for the colonizers, who would then encounter only limited resistance.