As a former submarine officer, I’m probably biased, so take the following with a grain of salt.
I would go with the Nautilus. It was the first true submarine, freed from the necessity of having to surface or go to periscope depth in order to recharge the batteries.
(Note that the Nautilus still had the traditional V-shaped hull designed for cruising on the surface; the teardrop-shaped hull had to wait for the conventionally powered Albacore, and the Skipjack was the first sub to combine nuclear power with the teardrop hull optimized for underwater cruising. Nevertheless, it was the nuclear powered propulsion alone that accounted for the revolutionary aspect of the modern submarine.)
We have never had a major naval battle since the era of the modern submarine, but in a true no-holds-barred shooting war, submarines would finally come into their own. Once hostilities ensued, I figure that every surface combatant on both sides would be sunk in about 15 minutes. The only naval vessels left would be submarines.
Much of the conventional wisdom regarding submarines seems to still have the WWII-era fleet boats in mind (i.e. slow-running submarines hiding from destroyers, popping up to launch salvos of straight-running torpedoes). While there have been great advances in ASW (anti-submarine warfare) technology since WWII, the advantages gained by the submarine have far outstripped those. The first indication that a typical surface vessel would have that a hostile submarine is in the area is the large explosion. Modern torpedoes have homing capability, and modern subs do not have to view the target with a periscope or use active sonar. Modern nuclear submarines do not have to wait for their targets to get within range. Their range is unlimited, and they also have a great speed advantage. Finally, in being submerged continuously, they have the ultimate stealth advantage.
The Soviets/Russians and the Chinese realize this, which is why their naval efforts in recent decades have emphasized submarine construction. And the most effective defense against a modern submarine is another submarine.