The title character. Nate is a sixth grade straight-F student, self-proclaimed ladies' man and Renaissance Man, and quite short (4'6" to be exact). His crush is Jenny, who hates him, and his sworn enemies are Gina and Mrs. Godfrey.
Anime Hair: At one point, his friends try to make fun of him by making an ice cream cone with ice cream that looks like his hair. Nate admits that while he's not happy with it, it is a creative use of "Hershey's Kisses."
Gina: Him being a slacker and her a kiss-up straight-A student, they clash very frequently. Nate's friends commented they have a Love/Hate relationship however.
Mrs. Godfrey: His social studies teacher. Somewhat onesided, he does not like her at all and they clash the most frequently. While most of it is Nate's doing, there are times where she also shows her frustration with him.
Randy Betancourt: The school's Top Jerkass. Whenevr he is messing with someone, Nate will usually be the one to step in and Randy is also one to retaliate.
Jerk with a Heart of Gold: Nate is often seen sticking up for those needing it and will give a helping hand in his own way (such as when a student is dealing with someone annoying or that's a jerk, Nate lures them to his locker and opens it, blasting them away with the crammed junk.) His reasons for not being nice as often might be a result of having a huge streak of bad luck.
Professional Butt-Kisser: It is mentioned that he has Mrs. Godfrey's birthday in his planner. Also, in the Jefferson saga, upon learning that they're going to Jefferson, Francis shows up in Jefferson garb.
Teacher's Pet: Is definitely in far better graces with teachers than Teddy and Nate.
Nate's other best friend, who matches Nate in prankster tendencies. On the rare occasions that anyone agrees with Nate, it will most likely be Teddy. His parents are mathematicians, as evidenced by his middle name being the square root symbol.
Hollywood Genetics: Guy with ambiguous hair color gets a raven-haired kid and a blonde kid.
Hypocritical Humor: Quite a bit. Examples include: Confiscating Femme Fatality when he has an Anna Kournikova screen saver, telling Nate to eat healthy when in fact he has a rather decent-sized sweet stash, etc.
Nate's older sister, who drives Nate crazy. Has grown to less significance as the strip goes on.
Pint-Sized Powerhouse: Frequently beats up Nate (at least in the earlier strips.) To be fair, he is usually provoking her when she tries to beat him up.
Averted somewhat. While she's shorter... this is compared to other adult characters, and only by a few inches. This can also be explained by her being a teenager still. Compared to Nate and his friends, she is about twice as tall.
Nate's teacher and Arch-Enemy. While not as evil as Nate often describes her (because only Umbridge could be that evil), often shows blatant favoritism.
Parental Favoritism: Quite blatant. A recurring gag is that Gina will answer a question (without raising her hand and usually with a loud "OOH!", but when Nate does the same thing, she shoots him down.
The novels seem to indicate that she far preferred Nate's sister Ellen over Nate. Given what sort of things Nate gets up to, that's not really a stretch.
Nate's long-running crush who is often annoyed and angered by him. Despite this, she manages to have something of a friendship with him. Is currently dating Artur. As of a 2013 strip, she has moved away to Seattle.
Lysistrata Gambit: Uses a (toned down) version of this technique to beat Nate at Monopoly.
Odd Friendship: Arguably, her friendship with Nate could be seen as such
Despite often not liking him, she goes to his house with the rest of his friends for Monopoly night.
A transfer student from Belarus, who is Nate's Foil. While he is probably the nicest character in the strip, he has a one-sided rivalry with Nate (from Nate's point of view). Has a severe case of Does Not Understand Sarcasm.
Provides Examples Of:
Always Someone Better: He is better at drawing and chess than Nate, two skills that Nate values the most about himself. The latter is addressed much more frequently though.
Unknown Rival: Nate has a massive grudge against Artur for being better than him in several things (particularly, chess and drawing, two skills Nate prides himself on). To make matters worse, Artur is not only better at them than him, he's so darn modest about it!
Nate's other arch-enemy, Gina is the polar opposite of Nate, getting straight A's and never letting him forget it. Basically, she's Ellen all over again, just a whole lot less ditzy.