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Susie Derkins asks Calvin to cheat and give her the answer to a test question in an early strip. After this, she is depicted as a serious student who resists Calvin's constant requests to help him cheat in any way.
In the early strips with Susie's first appearances, she and Calvin both seem to internally acknowledge that they have crushes on each other underneath their insults and animosity. This soon changes with Susie switching her affection to Hobbes and Calvin panicking over even the thought that Susie likes him.
Calvin catches Hobbes in a tiger trap in the first comics, and this was supposed to be how they first met. A later strip near the end of the comic's run, however, had Hobbes recall Calvin spent most of his infancy "burping up", hinting he had been with Calvin for much longer.
Calvin was shown as a member of the Cub Scouts in a few early strips. Watterson originally thought this would provide plenty of interesting scenarios for storylines, but quickly dropped it after he realized Calvin was not the sort of kid who'd ever join up with the scouts. The Running Gag of Calvin's dad taking the family on horrible camping trips filled the same purpose and fit the strip's atmosphere much better.
Likewise, the series of strips with Uncle Max was intended to open up storytelling possibilities, but Watterson realized how awkward it was to have characters interact with Calvin's parents without ever referring to them by name was and dropped the idea.
Garfield's wildly different appearance in the early years of the strip: much fatter, more cat-like, and strictly quadrupedal. There's also Jon's claim to be a cartoonist in the very first strip, which is rarely mentioned again, and the character of Lyman (Jon's roommate and Odie's original owner) who slowly vanishes entirely without explanation.
The early strips' humor also relied more on wordplay and topical references. Jim Davis gradually stopped using both once the strip got popular, feeling that their removal would help make the strip more marketable in other countries. Similarly, the tone of the strip also became more zany in the 80s and 90s before mellowing again in the 2000s, although in recent years it's slowly been edging back into zany territory. (Most Garfield connoisseurs would declare that the strip was at its creative peak roughly between 1985 and 1995, and in the late '80s especially.)
Dilbert was initially focused on the personal life of Dilbert and Dogbert, and was largely Garfield except with a dog who can talk. The office-based strips came a few months later and even then only occasionally appeared. They more or less took over a few years later.
Thimble Theater used to be about Ham Gravy and his manager until they hired a certain sailor named Popeye.
Rick O'Shay was a humor comic set in the 1950s and 60s until it transitioned to the 1860s and, while still having comedic elements, turned into more of a western adventure/drama strip with more realistic art.
Peanuts had a very different art style, far lighter humor, and a mostly different cast of characters (Shermy and Patty, not to be confused with Peppermint Patty). Charlie Brown was very different from the self-hating loser he'd later become: he was a cheerful kid who liked to play pranks on others and boasting about himself. Snoopy was just a normal dog, and he wasn't Charlie Brown's pet. Linus and Lucy didn't exist. (And even when they were added, Linus was a super-smart little kid as opposed to an Innocent Prodigy, and Lucy was a wide-eyed Cloud Cuckoolander toddler before becoming her Jerk with a Heart of Gold self.)
Early on, FoxTrot was a lot more realistic and down-to-earth family strip with only a few traces of "nerd" humor. Throughout the 1990s, it began gradually shifting more and more toward a less reality-based strip with greater emphasis on "nerd" humor, pop culture references, and satire. The shift in tone coincided with the art going from a more detailed and sketchy style to the flatter, stiffer, more "cartoony" look it has now.
In the early Zits strips, the art was less polished, and some characters were different. Jeremy's band had a black drummer named Y.A., who never really developed and quit the band early on; he was replaced by Pierce, who quickly became an Ensemble Darkhorse. Jeremy's mom was supposed to be a child therapist, but it was only brought up a couple times. His older brother, Chad, was originally a "perfect" guy whose face was always blocked by word balloons, before being retooled into a more "normal" character (but still leaving Jeremy as The Unfavorite). Another early trait that was soon dropped was having Jeremy be The Narrator.
Bloom County evolved massively. Early on, it was a bunch of people living in a boarding house, with Milo as the main focus. Over time, many details were fine-tuned, many characters (e.g. Limekiller) were dropped, and the strip shifted to the main focus of Milo, Binkley, and Opus the penguin. The art style was also very blobby and unrefined, with a different lettering style.
When it started out in the 1960s, The Family Circus had a radically different art style; PJ didn't exist yet; and the dad was more of a stereotypical deadbeat dad/buffoon type who smoked, drank, and wore a hat. His personality was overhauled to a more sympathetic figure, and the art was smoothed out come the 1970s.
Beetle Bailey started as a comic about college students. When it didn't take off the characters enlisted in the army on a whim. Sixty years later they have yet to graduate from basic training.