Mewtwo is a man-made Pokémon, created from the DNA of Mew. All the other cloned Pokémon in the movie Mewtwo Strikes Back look like the one they cloned from, but not Mewtwo. Mewtwo looks totally different from Mew. Why is this?
I believe this is a plothole, stemming from the discrepancies between Mewtwo's origins in the games, and its origin in the anime.
In the games, Mewtwo is not a clone of Mew, but actually its child: the journals in Cinnabar Mansion refer to Mew giving birth to it. Mewtwo was then subjected to "years of horrific gene splicing and DNA engineering experiments", which explains why it only vaguely resembles Mew - its DNA is no longer solely that of Mew.
In the anime, however, Mewtwo was cloned using Mew's DNA, and there is no mention anywhere of it being subjected to any further experiments, only of it "maturing" into its present form. Prior to maturing, it resembled Mew more closely:
It's still possible that Mewtwo was experimented upon in a similar manner to the games, but in the absence of any evidence, I have to chalk this up to a simple plothole: there is no clear explanation for why Mewtwo should differ so drastically from the Pokémon it was cloned from, when the other clones exhibit no differences besides dark splotches.
In the Pokémon Adventures manga, Mewtwo was given human DNA as well as Mew DNA so Mewtwo should look different then Mew. More human. I don't see why this couldn't also have been the case in the anime and games. However, the Pokemon that Mewtwo cloned were given hardly any changes but the change of that they would obey Mewtwo. They were not injected with human DNA but with Pokemon DNA.