At its core, Naruto is a story about a ninja, on a team of ninjas, fighting against other ninjas. Over the arc of the series, readers are introduced to a plethora of ninjas who command a mind-boggling assortment of powers and skills. Consequently, determining which ninja is the most powerful can be futile without some search limitations. Accordingly, the scope of this comparison focuses on those ninjas who are relevant to the future development of the series.
Naturally, being that he is the protagonist of the series, as well as a key character in the follow-up series Boruto: Naruto Next Generations, Naruto Uzumaki must be in any “most powerful ninja” discussions. Indeed, Naruto checks all the boxes for the definition of being powerful in the series. Naruto’s power is largely due to the fact that he is jinchuriki of Kurama, one of the most powerful of the mystical tailed beasts inhabiting the Naruta universe. Kurama gives Naruto tremendous levels of chakra, and over the years, the two have developed a relationship that has allowed Naruto to tap into the beast's chakra in a way unseen before. For instance, through the Nine-Tails Chakra Mode, Kurama gives over his full power to Naruto’s control, making him invulnerable to most physical attacks. Moreover, when applied during the Six Paths Sage Mode, Naruto is given a nearly limitless power boost as well as the ability to fly and avoid his enemies' best attacks and amplify any attack he conducts. As the current Hokage of Konohagakure, Naruto’s influence will be felt for many years to come.
In the manga, wherever Naruto goes, his lifelong rival and best friend Sasuke Uchiha is not far behind, or ahead. Throughout their lives, Sasuke has competed against Naruto and held his own. Even during the series finale when Naruto’s was at the height of his power, Sasuke fought Naruto to what could only be called a standstill. While Sasuke is not possessed by a tailed beast, he does have an abnormally high level of chakra. Like Naruto, this allows him to perform some of the harder jutsu with relative ease. As he grows older, he develops a number of other powers that increase his abilities dramatically. One such power is the dojutsu Sharingan, which gives him the ability to mimic an opponent's moves. Later, Sasuke also manifested Rinnegan, another dojutsu that allows him to master every known Jutsu, access the Six Paths Technique, shapeshift, and even open portals to other dimensions. As a top trainer of the Academy, Sasuke will influence the next generation of ninjas.
Outside of Naruto and Sasuke, the only other ninja that fits the scope of comparison is Orochimaru. While he is technically not a ninja any longer, he once was a member of the Sannin, perhaps the greatest trio of ninjas Konoha ever saw. While his quest for immortality eventually lead to his abandonment of the team, the village, and being a ninja, he nevertheless maintained many of his ninja skills and abilities. He also was one of Sasuke’s trainers. He influences lives through Mitsuki, an artificial human cloned from his DNA, who is a classmate of Naruto and Sasuke’s children.
So, who of the three is the most powerful? Naruto clearly has the edge. He might not be the greatest ninja of all time, but he is clearly the greatest ninja of his time. Moreover, he will be a major influence on the next several generations of ninjas who define themselves, their abilities, and the art of ninjutsu.