Orochimaru was the first Naruto villain introduced to be vastly beyond the skill level of anything short of a Hokage. Through his guile, treachery, and the jutsu he invented, he was able not only to slay Hiruzen Sarutobi, but he was also one of the few villains to survive the entire series and never face tangible retribution for his crimes.
Naturally, his creativity and elusiveness make him a severe threat even for the universe's most skilled shinobi, though there are some whose power eclipses his own. By analyzing the characters stronger than Orochimaru, it can be determined who could have ended his vile legacy prematurely.
10 Kisame
Orochimaru may be a competent fighter, though he relies primarily on his ninjutsu in order to win his battles, with such techniques as extending his body and summoning many minions to dispatch his foes.
Unfortunately for him, this would play right into the shark's hands, as many of his abilities are intended to consume chakra. It would deplete the fallen Sannin's energy rapidly, making his movements sluggish and leaving him vulnerable to become the swordsman's next delicious meal. To the Akatsuki, it would be especially satisfying, given Orochimaru's previous betrayal.
9 Hashirama
The First Hokage of the Leaf, Hashirama's immense skills were so great that they were able to overcome not only Madara Uchiha, but also the enslaved Nine-tails at his disposal simultaneously.
Senju could erect a massive wooden construct that successfully grappled against the Susanoo and inflicted widespread damage on the surrounding terrain. Given these accomplishments, it follows that he would obliterate any creature the Sannin could stir against him, even including the notoriously deadly black snake, Manda. The scientist's demise would follow shortly thereafter.
8 Naruto
Even as a child, Orochimaru struggled to contain Naruto's unbridled power when his Jinchuriki state was unleashed. Though he was volatile in this state, it discouraged the Sannin's attacks and ultimately made him unable to claim his treasured prize.
After Uzumaki's sage mode training had been completed and he gained Haguromo's boon, what was already a galling disparity in their strength became completely insurmountable. Now, the damage Naruto could inflict on a whim is potent enough not only to defeat Orochimaru but also to obliterate whatever new base he was hiding in simultaneously. The newly christened Hokage's destructive force overshadows any nuanced trickery the Sannin might devise against him.
7 Pain
Though Orochimaru had once operated well within the Akatsuki, Nagato's strength is on a completely different level than his own. This is demonstrated through his attack on Konoha, doing what the fallen Sannin had only dreamed of: obliterating the Leaf.
Not only was he able to accomplish this in a single attack, but he also fended off Naruto Uzumaki even though he was exhausted and would have defeated him if Hinata did not intervene on his behalf. It speaks to the terrible potential at the fingertips of Jiraiya's former student and proves the indisputable power of the Rinnegan.
6 Kabuto
While Orochimaru's techniques may have provided Kabuto the template for his own jutsu, the student far surpassed his teacher. It was especially true after the Sannin did not have time to practice his craft on account of his harrowing defeat by Sasuke Uchiha.
Not only was the former spy able to master the skills of the Sound Four, but he also trained with snake sages, learning powers which were much akin to Naruto's own. He became deadly enough to overwhelm Itachi and Sasuke at the same time, forcing them to resort to a forbidden technique for victory.
5 Itachi
Orochimaru may be no stranger to genjutsu, but he dramatically underestimated Itachi's ability to use it effectively. During his time in the Akatsuki, he had hoped to ambush his "partner" and steal his Sharingan, only for the tables to quickly be turned.
It would result in the Sannin's mortifying defeat and banishment from the organization. Should the elder Uchiha have learned of the snake's intentions with his brother, it's unlikely that he would have allowed him to survive their first encounter.
4 Hiruzen Sarutobi
It is true that Orochimaru was ultimately able to defeat the Third Hokage during their memorable battle on Konoha's rooftops. However, the Sannin had prematurely prepared the Edo Tensei forms of Hashirama and Tobirama, giving him an unfair advantage that he would usually never have in battle (since the ritual takes time to complete).
Given that Hiruzen had performed well against his former pupil up until that point, it follows that without this edge, he would not have been nearly as successful, a fact which the scientist counted on when forming his original strategy.
3 Madara
There are few shinobi in history more skilled than Madara Uchiha. After his resurrection, he promptly began to slaughter hundreds of shinobi, decimating an entire army and later all five Kage at once (which in contrast, Orochimaru struggles to defeat even a single one).
In his later form, the patron Uchiha even became immune to ninjutsu and genjutsu, forcing his adversaries to use taijutsu to have a prayer of defeating him. Given that it's handily the Sannin's weakest skill of the three, he would not pose a shadow of a threat against the vengeful ninja.
2 Konan
Konan may not have fought as often as her Akatsuki brethren, but her talents were just as commendable. She was able to disperse herself into paper bombs or cast them at an enemy, each of which inflicted devastating consequences.
In her fateful fight against Obito, it was revealed that she could control up to 10,000 of these explosives at once, detonating them consecutively for up to five minutes. It would provide a threat that Orochimaru would have no hope of overcoming, especially since his skills orient around averting damage rather than withstanding whatever attacks are dealt against him.
1 Might Guy
Easily the most skilled taijutsu master of the entire series, Might Guy's unimaginable physical speed and prowess would overwhelm Orochimaru in minutes if not seconds, depending on how many gates he opened.
Guy has demonstrated resilience against genjutsu, as seen through the infiltration of the Chunin Exam. It follows that such treachery would not work on him, forcing the Sannin to resort to ninjutsu attacks that he would invariably dodge with ease. Even if Orochimaru summoned Manda, Rock Lee's mentor has displayed the strength required to bring the beast to heel with only a handful of sturdy punches.