Here's my top five:
1) SEO and AdSense. Learn 'em. Really, this could be points one through five.
2) Focus your marketing attention on the pain point your software/service addresses and how their lives will improve as a result of using it (benefits), not on what your software/service does (features).
3) Instrument freaking everything and remove anything which causes more people to fail at whatever the core task of your application is. If you do this, you will find places where your view of the world is so different from your users' that you could not possibly predict what their issue would be. e.g. for the significant percentage of your users who think Google is the Internet.
4) Email is the single best way to maintain your relationship with someone when they're not on your site, which is most of the time.
5) About 1 million people Tweet. Some 3 millionish people subscribe to Techcrunch. Twenty million voted for Ross Perot. Please recalibrate your understanding of what broad mainstream appeal is.