Free Will
The overarching question of this novel is the age-old debate between free will and determinism. It seems like the characters of The Sirens of Titan have the free will to choose their destinies, but the predictions of Winston Niles Rumfoord always come true (except when he's lying), regardless of what the others try to do to avoid them. Further playing into this issue is the revelation had on Titan near the end of the novel, where Salo the robot explains how the Tralfamadorians have been mind-controlling humans to do their bidding since the dawn of humanity, creating the Great Wall and the Kremlin to send messages to Salo, which makes human history seem nearly meaningless.
Randomness
Almost everything that happens in this novel is completely random and/or arbitrary. Malachi Constant's father, for example, attained his immense wealth by opening up a Bible and taking the first two letters from Genesis and investing in a company with those initials, repeating this process until he finished the whole sentence and found himself incredibly rich. Other such examples pepper the text, with Rumfoord's random state of wave-like existence and Constant's recruitment into the Martian army. There appears to be a lack of grand narrative in this novel, being driven entirely by chance, making randomness one of the most dominant themes.
Criticism of Religion
Vonnegut isn't one to be shy of lambasting religion, and this book, although not quite as brutal as Cat's Cradle, doesn't pull many punches. Christianity is satirized in Constant's father's use of Genesis as the genesis for his incredible wealth, although not quite as bitingly as in Rumfoord's creation of his new religion, the Church of God the Utterly Indifferent. This religion is a parody of Christianity, mocking God's seeming indifference to what goes on in the world today. Also harsh is Vonnegut's portrayal of Malachi Constant's (whose name is a tongue-in-cheek biblical allusion as well) "crucifixion" and "ascension" as he is banished from the planet Earth and sent upwards to Titan, where he learns that the entirety of human history has occurred in order to send a small self-destructive robot a piece of scrap metal, the ultimate joke in the face of a religion that preaches ultimate meaning.
