ReBoot/WMG

Phong knew all along that Enzo, AndrAIa and Friskit survived.
In "Number 7", Matrix's dream/nightmare was created by Phong through some psychic connection, similar to with Dot in "Identity Crisis, Part 2". The dream Phong is the REAL Phong.

This may have happened inadvertently while Phong is being tortured by Megabyte.
 * Or, maybe it was the result of what Phong did to Dot? The device was supposed to send waves into the past and future. The past effects we saw, Dot hallucinating, but maybe this was the future waves? Maybe this is when the flash forward Dot was having would have actually taken place?

Mainframe's User is a little kid.
Plays games all the time, never erased the RAM which spawns the game characters in System Crash, only updated the system files once, never ran a virus scan before the system crashed, didn't even try to fix the system when Megabyte destroyed it, and after the system crashed he only types YES when the computer asked for a system restore. The user was simply to young to know how to do anything on a computer other than play games.
 * You do realize that the user only experienced 2-3 days over the course of the show's entire run, right? And updates tend to be done automatically when the system is online.
 * In that case, the User has been playing a metric ass-ton of games in that little a time. Maybe the game cubes represent flash games?
 * Neither the updates nor flash games were popular when the series was made.

Games are only harmful to systems that already have a viral infection
That is, games only compound the system errors caused by Viruses, the most common and prominent of which is Nullification. Systems that are clean don't have anything to fear from losing games but viruses are so prevalent and the effects of their infestation are so ingrained into public consciousness that no system dares running the risk of losing a game.

Mainframe does not have one User
But several, it's a family computer that everyone is taking turns using and playing with. This is why the User seems so inconsistent, there is actually one one tech-savvy person in the family and everyone else is screwing around, playing games, downloading viruses from the net and generally causing problems for everyone else.
 * It's also possible that Mainframe is a public computer in a school or library that the patrons are using improperly.

ABC was afraid that CGI would take over Western Animation.
All the Executive Meddling ABC did to Re Boot was an attempt to force the show to fail and kill the medium before Follow the Leader took effect and spawned a wave of CGI shows that would replace traditional Western Animation. While Re Boot survived the meddling, ABC succeeded in preventing Follow the Leader and delayed the wave of CGI shows for about a decade. ABC's motive for this was to maintain the Animation Age Ghetto by preserving the Status Quo of Western Animation.
 * Mainframe also ended up making Beast Wars only a few years later in syndication, which helped popularize the idea of an all CGI animated series and led to the boom in CGI animation that persists to this day. With Beast Wars they still had Executive Meddling to deal with, but it seems almost kind and good-natured compared to some of the hoops Reboot had to go through, and most of that was because there was franchise history and continuity to deal with rather than outright censorship.

The User is a genuine Eldritch Abomination.
And I don't mean on a Humans Are Cthulhu scale. Nothing the User does and nothing about the Net and the Web make any sense when applied to our computers. It's easier to believe that sprites and binomes are human-scale entities in a universe run by creatures that would drive real-world humans mad on sight.
 * Alternatively, The User IS Cthulhu, and Mainframe exists in an Eldritch Computer that follows a completely different set of rules that don't make sense to us, but make perfect sense for Cthulhu.

Hexadecimal isn't a true virus
She's a living viral upgrade. When Kilobyte upgraded to Gigabyte it was stated to have skipped a generation. However, as it was upgrading it was teleported away by Welman Matrix and seperated into two viruses. Megabyte is the real virus, the skipped generation, strong, persistent and infectious. Hexadecimal is the interrupted upgrade, she's raw power given form, her chaotic behaviour is due to a lack of purpose. Notice how, throughout the entire series, Hexadecimal lacks a function, no other character has this problem. Every single virus we see is on a mission to infect or destroy but Hexadecimal just sits around until she gets bored and then stirs up some trouble, not even seeming particularly bothered when she is ultimately thwarted and even switches sides without much thought or effort. Further notice that Gigabyte really is little more than Megabyte with Hexadecimal's powers.
 * Unless spreading chaos IS her function. It would explain why Gigabyte doesn't have the exact same function as Megabyte. Function: infect and conquer + spread chaos = destroy systems.

Mainframe's User rents all of his/her games.
Assuming all of those games run off a disk and are not installed into the computer this explains why the User rarely plays the same game twice. He/She rents a game, plays once and loses, says WTF this game sucks, and returns the game immediately.

Number 7 Wasn't a dream.
That system was really a Playstation and The User had loaded the Re Boot video game for the console. But since Matrix was in the game Recursive Canon kicked in and destabilized the game code. As Matrix derailed the game looking for the Number 1, the game code continued to deteriorate and all sense of logic was lost, resulting in a Mind Screw. Matrix's "chat" with young Enzo finally crashed the game and rendered Matrix unconscious while the User went back to playing a golf game. Being a game sprite Andraia's memory was reset when the Re Boot game crashed and had no idea why Matrix was unconscious, and decided to tease Matrix by saying he was knocked out by a golf ball.
 * AndrAIa wasn't teasing him, he actually had a lump on his forehead from where the ball hit him.

Daemon was the Y 2 K bug.
Think about it; a virus threatens the entire net and is going to cause the entire thing to crash, at a specific time. At the end of the day the virus disappears and no systems crash at all.

The User is The Angry Video Game Nerd
I can just picture the user being AVGN reviewing awful games. He could be complaining about The Computer Is a Cheating Bastard and Game Breaking Bugs. That also explains why he never plays the same game twice: he destroys the ones he thinks are bad

Hex isn't exactly dead
I mean, how can she make the closing narration if she's dead? In memory of Hexadecimal. Format - Virus: Savior of the Net.
 * That's right. She's just stuck at TVTropes.

Matrix's Eye can read sprite code
That's why he took an instant dislike to Ray Tracer. He was hope to stop him from meeting Andraia, since what he would do then was written all over his code.

There was no retcon of Bob's backstory
Just because he originally went to Mainframe earlier than we thought doesn't mean he stayed there. We saw the other Guardians show up shortly after he followed Kilobyte's signal. They likely cleaned up the damage caused by the explosion and took Bob back to the supercomputer to finish his training. Bob finished his training and went on to be a great Guardian, catching Mouse and earning himself a great reputation which in turn caused Turbo to grant him the opportunity to test his theory in Mainframe.
 * His deleted partner kept on refering to him as Cadet, so it's pretty obvious that he didn't stay in Mainframe.

Matrix spared Megabyte in Showdown because of the episode Talent Night.
Because in that episode, Megabyte gave Enzo a guitar for a birthday present. After rocking out with it for absolutely no reason other than "I've always wanted to do that". It was just barely redeeming enough to justify sparing Megabyte one time.

Mouse is the avatar of a User
If I recall correctly, Mouse was stated to be a hacker. And if we assume that Reboot terminology is consistent with rel life terminology, that would make Mouse a true hacker. (leap of logic goes to Trinity from The Matrix before she woke up?) As a result, she IS a user and her appearance is merely an avatar to prevent the denizens of Mainframe from effectively looking at an Eldrich Abomination.
 * The disguise is nowhere near perfect. She has fangs, and her "hair" is red static.