I think that this is interesting because of the way that it makes something (the background) that was not supposed to be the main focus of this video game the only thing that you see. If you have some cultural knowledge you sort of can tell that these clouds are at least from a video game, although many people will probably find them distinctly Mario-esque. To watch video game clouds move on a blue background sort of gives you the sense that you're waiting for something to happen. And nothing else happens. There's a disconnect between what you expect to be there and what is there, so you have to reevaluate your expectations.
Others artists have dealt with the idea of clouds in their work. Clouds are interesting because there are a lot of ideas as to what they are supposed to look like but they don't necessarily always look so cartoony and perfect. Clouds never look like the ones that Cory Arcangel has created, but you still know what they are.