"We dreamed of creating the world's strongest Pokémon...and we succeeded." -Dr. Fuji
The Pokémon, the myth, the legend, Mewtwo is a force of nature that was truly the strongest in Gen I, though years of power creep have dethroned it from the very top. Make no mistake, Mewtwo can and will destroy you given a chance.
The End of All Things
Mewtwo
Ability: Pressure/Unnerve
Item: Life Orb/Focus Sash/Heavy Duty Boots
-Nasty Plot
-Psystrike
-Shadow Ball
-Aura Sphere/Fire Blast/Ice Beam
Nature: Modest (+SATK, -ATK) or Timid (+SPE, -ATK)
EVs: 4 HP/252 SATK/252 SPE
...begins with a Nasty Plot. A simple boosting Mewtwo, one Nasty Plot guarantees Mewtwo (Timid Life Orb) 1 or 2HKOs everything in the game depending on its coverage. Psystrike is an absolute nuke, being a STAB move that targets Defense (so no Assault Vest, Blissey or Kyogre will save you) sitting at a base 100 before STAB. Shadow Ball is a hard recommend as the games Mewtwo runs around in tend to be infested with Psychic types that can stomach a Psytrike easily, but if you are in a metagame where Psychic types are not as prevalent, there are several other options. Aura Sphere hits Dark types like Tyranitar and Darkrai hard, while Fire Blast melts Steels (mainly Zacian Crowned) and Ice Beam just has fantastic coverage against many Flying and Dragon pokémon.
Mewtwo's base 130 speed is only beaten out by a select group of Pokémon: (Calyrex-Shadow, Zen G-Darmanitan, Dragapult Pheremosa, Regieleki, Zacian [both Crowned and Uncrowned], and Zamazenta) so once Mewtwo gets going, it is very hard to stop. This speed also gives Mewtwo some added utility as a revenge killer before it is time to sweep.
Item is up to preference. Life Orb enables Mewtwo to nab those needed KOs, Focus Sash ensures that Mewtwo will live to setup, while Heavy Duty Boots prevents entry Hazards from chipping/slowing Mewtwo.
Nature and EVs are standard Sweeper Array, maximizing offense and speed.
Dynamax
Mewtwo can easily abuse Dynamax, as a Max Mindstorm setting up Psychic terrain protects Mewtwo against priority as well as boosting its Psychic STAB to levels so ludicrous that words fail to explain them. The added bulk is also appreciated and Mewtwo's above average Base 101 HP becomes significantly bulkier after a Dynamax to the point that only Specs Calyrex-Shadow Rider threatens the OHKO from full health. However, Mewtwo's other moves offer little benefit to Mewtwo directly, so more often than not you will be spamming Max Mindstorm or the appropriate coverage move.
Mewtwo heads are better than One
Mewtwo
Ability: Unnerve
Item: Life Orb/Twisted Spoon
-Expanding Force
-Aura Sphere
-Fire Blast/Shadow Ball/Ice Beam
-Taunt/Protect
Nature: Modest (+SATK, -ATK) or Timid (+SPE, -ATK)
EVs: 4 HP/252 SATK/252 SPE
Pair Mewtwo up with a Psychic Terrain setter like Tapu Lele or Indeedee-F, and watch as Mewtwo lays waste with the 3rd strongest Expanding Force in the game to the opposing team with Psychic Terrain protecting it from Prankster and other priority attempts. Aura Sphere is the hard recommend here as Incineroar, Tyranitar and Urshifu Single Strike are very popular and can be expected to be seen. Coverage move is up to preference on who you want/need to hit. Mewtwo has a very fast Taunt that is great for stopping Protect/Wide Guard and other forms of disruption/setup, while Protect is simply great in doubles.
Unnerve is the ability of choice here as berries are far more prevalent in VGC and preventing a healing berry from going off is the difference between nabbing a KO or letting that pokémon survive and setup.
Other Options
Focus Blast -Wherever I suggested Aura Sphere, Focus Blast is also an acceptable option if you are fine living with the miss chance.
Flamethower -An option whenever Fire Blast is mentioned, though the power drop is noticeable
Trick -Mewtwo can pull of a classic Trick/Choice item set to great effect. Use Scarf to get the drop on Pokémon that would naturally outspeed it or Specs to blow holes open in the opposing team, then send it off to a wall to ruin it.
Hurricane -Popular option for giving Mewtwo a wicked Max Airstream, but does not provide much coverage outside of hitting Urshifu-Single hard.