I was 21 in 2008, and I'd been a fan of Ctrl Alt Del since near it's beginning. I was a huge web comic fan in general, and I got intensely emotionally invested in them, even the silly ones.
This strip hit me exactly as he intended it to. It resonated with me I guess because of my brother and sister in law going through a miscarriage shortly before. Either way, it had a powerful impact on me and I didn't see this "tonal shift" as a problem. That's kinda dumb if you ask me, lots and lots of comedies have serious moments.
Anyway, I didn't know this meme until a few years ago and it always makes me sad. It's dumb, I know.
I'm super sensitive to negativity, which is why I was always a lurker in reddit, I always got shat on whenever I shared anything, to the point that I'd just delete my account and hide from the internet for a while.