If you can illustrate a pun in a clever way, many times those go over well on this site. Or yes, things with double meanings are cool too. If you go for something serious, it usually has to be very pleasing to look at, or excel at whatever message you are trying to convey.

My recommendation is you should go rate a large number of the designs that are up, and pay attention after you rate a shirt to what the current average score is (and how many people have rated it). Then, go browse the shirts that are currently for sale.

I have noticed as I have been doing this, that this site is significantly more mainstream than it ever used to be. When I used to browse in college, nerdy things went over incredibly well, because the site had a much smaller fan base. Nowadays, Threadless advertises a lot more, and many many people have decided to try their hand at winning money from the site. The tastes of the site still lean towards nerdy/clever, but there are a lot more "normal" people that visit the site, so I would not be surprised to see something trendy based on pop culture pulling high numbers.

Something original, clever and/or it looks really awesome. that's it.

But pictures of my face are currently trending on Twitter. #myface.

Thanks, I guess that's a start. :)