I'm a big fan of Saturday Morning Breakfast Cereal, a webcomic.

Not lesser known but my favorite: Gary Larson's The far side always gave me a chuckle.

Poorly Drawn Lines.

I highly recommend The Perry Bible Fellowship

Well, if you’re looking for unrelatable and occasionally disgusting comics, check out mine. 😎

Back at the turn of the millennium I remember enjoying 1/0 by Tailsteak. I'm glad to see that it's still available.

I loved "The adventures of Oscar Zahn" great read. Alternatively if you have never read Garfield there is a bot who posts all the strip in chronological order over at Garfield@lemmy.world

Also before "The odd ones out" made his weird and abstract comics, he did actually make a funny little series similar to the peanuts

Falseknees makes gorgeous comics about birds. Each strip feels like art

Work chronicles makes funny corporate related strips but has inconsistent posting

Rustledjimmies made some great comics in the past but I haven't heard of him in a long time

I think you’re going to have to dig into the wayback machine (because I don’t think they’re actively hosted anywhere anymore?), but Nothing Nice To Say by Mitch Clem was a great punk rock web comic from the 2000s.

Newspaper style comics specifically? Maybe Fraz. Revolves around a janitor working at an elementary school. I haven't kept up with it but the creator cites Calvin and Hobbes as an inspiration and I love what I've read so far.