When I started posting comics on the web (for example, Lifehouse BVB), I used a traditional newspaper strip-style. These kinds of comics usually have 3 or 4 panels, and deliver some kind of punchline at the end.
I don't know why I used that format - I wasn't really thinking of it as a webcomic, I was thinking of it as a comic that I wanted people to see. But it fit with the little gags and allusions that I wanted to portray, and I don't like to use more panels than I need to to get the point across. I notice that a lot of humor-style webcomics still use that format, and full-page webcomics tend to be the more serious type.
I started Think Before You Think as a humor-style comic, and I wanted to use a 6-panel layout so I could do more with the humor than just deliver a punchline. I think in some cases, the first 3 or 4 panels of one of the pages could stand alone as a traditional old-school gag comic, and then I use the rest of the panels to either extend the joke, deal with the aftermath, or just something random and unexpected, and I think the result makes the characters seem more real, and presents different levels of humor.
It's the type of thing I see more in TV than in comics, because TV shows actually have the space and time to flesh things out.
One of my friends told me that one thing he likes about my comic is that he never knows which panel is going to be the funniest. And maybe it's just that my conclusions are lame sometimes, but I like to use the whole layout, and squeeze as much entertainment as possible into the 6 panels.