Please don't list this on a work's page as a trope. Examples can go on the work's YMMV tab.
Tear Jerker: Brawl in the Family
Make sure you've read all the Waluigi in the Family strips, then read the Waluigi Trilogi, where things get even crazier. Then, reach the bottom and realize you are a horrible person for judging Waluigi so harshly.
In real life: Matt, after having to postpone comic 400 for about a week and a half due to health problems, finally told us just how bad it was. The emphasis he puts on the pain he's in is staggering.
Even though it ended with a joke, The strip End◊. Kirby's "It's too hot" just brings a tear to the eye for some reason. Of course, YMMV.
Apparently, Matt made it during a Creator Breakdown after his Wii lost all of its data. So really, the comic is mirroring what Matt feels happened to him: all of his favorite adventures and characters have been destroyed. It really shows the affect games can have on people and why they're so important to us.
While the Mushroom Kingdom Carol has its hilarious moments, it's heartbreaking to see Mario change from his jovial, happy self to a bitter, cynical miser in the years since losing to Bowser ( really Jr). Luckily, he snaps out of it..
Comic 515. Another tribute comic, this time, to the legendary Hiroshi Yamauchi.
Comic 517 is, while funny, a little heartwrenching when, at the end, Sonic has his "Blue Blur" nickname stripped from him and given to Mega Man. Played for Laughs though it may be, anyone who's ever dealt with the Always Someone Better trope in real life and had a similar situation will sympathize greatly.