On the surface, this film looks to be more or less a Gary Larson gag stretched out over the course of an entire film. But in reality... that's... not far from the truth, really. But it's decidedly better than it sounds, provided you have an appreciation for 50's sci-fi films in the first place. The paranoia and xenophobia are extremely over the top, but like so many other things, this is done deliberately to invoke the kind of xenophobia films of that era tended to have.
In essence, Planet 51
is a mixture of 50's B-movie parody, 80's buddy alien film, and a whole lot of role reversal.
In actuality, while the role reversal element is played up, it's not the only thing to hold up the movie. Indeed, one could swap the aliens with the humans and you'd still have a decent George Lucas Throwback/parody. The characters fall into archetypes, but manage to be reasonably likable, provided the slapstick doesn't turn you away.
All in all, this is the kind of film best reserve for family night, or for those who have a taste for the genre. But for that demographic, it's definitely worth a look.