The series is a parable about the difference between wanton pleasure seeking and true freedomThe series leaves a lot of room for interpretation, so a lot of this is my own guesses. The series begins when he meets Shark, but this isn't the first time they have meet. In fact Fitz has been wandering around a for an unknown length of time, generally being an amoral pleasure seeker. How ever, this cycle Fitz begins breaking the masquerade. Slowly, Fitz comes to care more about things and in the end stops believing his probably illusionary wife and daughter and is more motivated by caring for his only constant companion, Skillet. This process destroys the control of the increasingly decadent Shark and Rectangular Business Man, who represent the Military and Industrial complexes respectively, which represents their inability to control the Older and Wiser Fitz.
The series is a later season of Big OEvery reset of Paradigm City degrades it a little, making it less realistic. Over dozens of resets, tomatoes became corndogs, Big O became Corndroid, and humans became whatever the heck the Twelve Ounce Mouse characters are. It all ends in another reset, but with hints that this time Roger/Fitz has learned how to break the cycle or at least alter it.
Amalockh's Breakdance of Death nullified Shark's and Liquor's bulletproofing.The order of events gets muddy due to the non-linear episode order, but both Shark and Liquor were demonstrably bulletproof before the Breakdance. Afterwards, Shark was killed by a barrage of bullets and Liquor was afraid of Robogirl's guns ("I'm boned.").
There are approximately 1440 simulations.Shark talked about "owning" a specific chunk of time, and if he owned the entire simulation, then he'd own all the minutes and not just 2:22. The "real world" is in fact simply a higher simulation which acts as a "lobby" between the different minute worlds. Time beginning to move may represent breaking that tiny little chunk free of the overall system control. Of course, being it's also a simulation, that may mean Shark and RBM are Not Quite Dead... again. And of course it leaves the problem of Upper Management.
Fitz's Wife and Daughter were there the entire time.In one of the, most likely fake, flashbacks we see Mouse's daughter turn into Spider. This one was literal; Liquor has established that Shark was working on turning other creatures into spiders in Q109, and it was a handy way to remove an unwanted element while testing the experiment. His wife, on the other hand, was Roostre. Or more specifically, the male green spirit possessing/guiding Roostre. Midway in, we see the Woman first turn into a man after eating a strange flower in the desert, with Shark watching. She is able to change at will, but he removed that feature before using it on Fitz's wife. Afterwards she became disembodied in the same way as Archeus. Near the end, Amalockh picks a flower, and shark reacts in shock. Stating that if that flower finds the right person, it will destroy everything. For some reason, it is essential to the plan that Fitz's wife remain male, perhaps simply so that Fitz will never suspect it's her, and possibly for a more esoteric reason.