"Simple" may be the first adjective to come to mind when discussing this set, but "strong" isn't too far behind. Once Mewtwo finds an opportunity to sneak in a Calm Mind, its massive Special Attack, Speed, and coverage will do the rest. Unless the opponent has one of the very few checks to Mewtwo, he or she will probably lose at least one Pokemon.
The chosen moves give Mewtwo the best coverage in general. Psystrike works as a generic STAB move and is Mewtwo's best attack against Chansey, Blissey, Kyogre, and Ho-Oh; however its main draw is that it essentially allows Mewtwo to work as a mixed sweeper, since it calculates damage based on their Defense stat, while still working off Mewtwo's superior Special Attack. Ice Beam hits Lugia and the Giratina formes hard, while Fire Blast and Aura Sphere both thrash Steel-types who resist Psychic and Ice. The choice between Fire Blast and Aura Sphere depends on the threats you need to cover. Fire Blast will put the hurt on Jirachi, Bronzong, and Metagross while Aura Sphere dents Dialga, Tyranitar, Heatran, and Dark Arceus. It is worth noting however that Fire Blast is boosted by sun and weakened by rain. Depending on what weather you expect to battle in, you might want to emphasize or forgo Fire Blast. Finally, should coverage be your primary concern, you can use all four attacks without Calm Mind.
Options: The EVs are as simple as the set's concept. It is unfortunate to lose the Special Attack boost from a Modest nature, but with Darkrai, Shaymin-S, and Arceus lurking in the Speed tiers right below, Mewtwo really has no choice but to go with Timid.
If you are using Fire Blast, it may be wise to have Groudon on the same team. Not only does the sun boost Mewtwo's Fire Blast, it also removes the rain an opposing Kyogre might bring. Mewtwo is vulnerable to all entry hazards, and Toxic Spikes in particular wears down Mewtwo quickly, especially when added to Life Orb recoil. As such, a Toxic Spikes absorber or spinner is a good investment. Forretress can Rapid Spin as well as lay down hazards of its own, while Tentacruel, Venusaur and Poison Arceus can absorb Toxic Spikes. Depending on the coverage moves chosen, Mewtwo will have trouble with certain Pokemon. A full list is given in the Checks and Counters section below. Solid answers to all these Pokemon are recommended. Finally, many teams rely on Choice Scarf Pokemon to revenge kill Mewtwo. As such, paralysis support coming from Pokemon such as Grass Arceus and Jirachi can be very useful. Wobbuffet can also trap and remove Choice Scarf users, paving the way to a clean sweep.
This is a good moveset for mewtwo (Pokemon #150) with the pressure ability/trait, a Timid nature, and equipped with Life Orb submitted by Cybermewtwo. For use in competitive Pokemon battles featuring an Export option and breeding guide.