This tip is simple. Build in all the functionality of your website/application before you start doing cool GUI/AJAX and all kinds of other features. If you launch a site and half your users cant use it cause they prefer Firefox then not only can they not use your stuff but its likely they will not come back and try it again.
When Microsoft Adcenter launched unless you were using Microsoft Explorer you were screwed. Now not only did that not allow anyone with Firefox but it also canned everyone who uses Linux or Mac OSX which is a pretty big margin IMO.
So anyway I dont want to pick on Adcenter its just the first example I could think of off the top of my head. Point is you need to really focus on functionality and usability. When you nail this then go for some icing in the user interface if you think its needed.
Just look at the enormous success of Cherrytap almost 1 million users already. IMO its the next big thing and yet it manages to do it without the coolest graphics ever. Another great example is Markus Frinds PlentyofFish dating website. Very simple looking sites that have awesome functionality.
So Focus On Functionality! Your SM Tip For Success #16