One of the essential motifs of the novel is the fact that Gregor has turned into a bug. What are the qualities of a bug that make this unappealing? What aspects of Gregor's life made him feel like a bug in his human life? The idea of being small, insignificant, and yet industrious all apply to Gregor. On the other hand, how do we generally feel about bugs? We tend to think they are gross, pesky, and to be exterminated. That is exactly how the family comes to regard Gregor. One of the most interesting facets of the novel is the fact that Gregor doesn't ever wonder how this happened to him. His acceptance and accomodation to his metamorphosis are remarkable. In the end, the novel is as much about how Gregor's metamorphosis affects him, but more importantly how it affects his family.
What a great question. One of the most exciting things to do with literature is to compare a text with what was done before. If you do this, then you can take a look at the original metamorphoses by Ovid, the Roman poet. I am sure that Kafka knew and read Ovid. So, what he does with Ovid is extremely interesting. One of the things that Kafka does is to show that metamorphosis is not a way of salvation, like many of the characters of Ovid. Instead, Kafka's work is dark and devoid of salvation in any sense. Gregor turns into a bug, his family is not even really surprise (which is surprising!), he dies and and his family moves on. It is as if the metamorphoses did not even happen.
To add on to the last answer, taking the first answerer's point a little further, I would like one to judge the way Kafka uses the Ovidian motif. Is it a parodic use or a pastiche of sorts. Put in a non-theoretic way, is it trying to mock the Ovidian structure or just reproducing it in a 'blank' way so as to repeat it?
Other important issues and themes to keep in mind are--
1. The theory of Absurdism--man as living in a world where meaning has cancelled itself via replication and proliferation. Man's life has become pointless. Gregor's changeover is sudden, arbitrary and absurdist.
2. The fracture of the family-relationships
3. Man's rationality being sardonically replaced by mere animal instinctiveness.
4. The theme of alienation and solitude
5. The biblical sub-text of the Fall of Man that runs through the story is something to take note of. For instance, keep in mind the scene where the family members throw an apple on Gregor's insect-body and it sticks to it. It is a tragic farce that reminds us of the spiritual variety of anguish that Kafka's frustrated divine quest implies.