Alternate Universe: Years ago, Scott ran a brief (very brief - like, not even into double digits) comic called (VGKitties), exploring the notion that Leo and Aeris were ordinary housecats interacting in housecatty ways, rather than a pair of funny animals.
Also used in one of the actual comics, which depicted an alternate universe where Sonic was more popular than Mario, Mortal Kombat (now "Minor Konflict") was family friendly, and the eponymous cats were now dogs with their roles in the comics swapped.
Anthropomorphic Shift: Early strips seemed to indicate that Aeris and Leo belonged to and lived with Scott, despite being anthropomorphic. Eventually it shifted to the two of them living independently as apparent college roommates, and in 2013-14 flashback strips showed them as children living in fully humanlike houses with their families.
Arc Welding: #334 and #335 both take place in the same era (when Aeris and Leo were kids) but are unrelated. #336 ties them together and shows the aftermath of each story (Scott even says this was an arc weld as he hadn't set out to do a three-parter but changed his mind after writing the first comic).
Art Evolution: Here is the earliest appearance of Aeris and Leo, back in 2001. And this is their early-2010 appearance. Yeah. Character style varies wildly from strip to strip.
Pantsman hasn't shown up in quite a while, and increasingly, Aeris is becoming Ramsoomair's megaphone.
Author Tract: "Nerd Rage", an entire strip consisting of a tirade on how casual gaming is ruining the industry. Lampshaded here where other characters point out that flat out explaining your points makes a shitty allegory, though that didn't stop him from dedicating seven panels to it.
Spoofed in one issue (#311 "Dress Rehersal") where Aeris and Leo, who are already dressed as Princess Peach and Luigi, are asked to put on the cat suits from Super Mario 3D World over top their existing costumes.
Defictionalisation: The "Wright for Life" comic led to the actual Spore team creating their own◊, replacing the drawn aliens with ingame ones, and later on physical models were made. Of course, Spore players can attempt something like this as well.
Don't Explain the Joke: Aeris's response to Leo when he makes an incredibly misogynistic joke about why girls like stories about vampires and feels the need to spell out what he's talking about. Leo does this a lot. "Recurring, if you will."
Double Entendre: "That is the BIGGEST barrel I've ever seen, is it pump action?"
High-Pressure Blood: This comic shows a Worms game going on... normal, right? Well, when part of the ground was destroyed by a rocket, we cut to... Leo in pain and blood stains behind him. Take a wild guess what happened. Also counts as Bowel Breaking Bricks when you think about it.
Mundane Solution: When playing Five Nights at Freddy's, Aeris pokes holes in the whole scenario, and rattles off several simple ways to counter the robots: dressing up in animal costumes to fool the robots, which is redundant as Aeris and Leo are furry animals to begin with, turning off some of the extra equipment to save power, or guarding the building from outside.
Orphaned Series: Not the main strip, but Adventure Log stopped at eleven strips and was deadlinked over a year later. According to Ramsoomair, the Adventure Log update schedule was directly tied to each release of the official Final Fantasy XI newsletter (which included the comic as an insert). The game always had rather shaky support from Square, and when they stopped making new newsletters, Scott stopped making new comics.
Aeris's color and "hair" style are the only real indicators that she's female. There was one comic, years ago, where both she and Leo were more humanly proportioned. This is the only recorded incidence of Aeris having breasts of any sort.
These days, it shows better that she's just 'small'. There's even a one-strip fancomic on-site that shows her as a bit self-conscious about it when she hears that a fictional Japanese adaptation gives her character a bigger bust. So much so that she tells Leo to bring his Pyro suit.
She looks like she's going to college, given this strip.
The first published version of this strip indicated that Leo was 21 years old; Ramsoomair later edited the figure to the less precise "many years earlier", as Leo himself has yet to reach that age to begin with.