The focus of the last couple of years - especially YC type startups - has been on social - which is pretty much saturated now (I laughed/cried at some of the content on that dreamitventures site that was posted yesterday).
We're in a recession now that means big opportunity for replacing established business software apps - because existing apps have grown bloated and carry huge costs - which gives a massive attack surface - a startup can do take an existing app and do the key features better, cheaper and simpler - and instantly bite in to some revenue.
New startups need to be taking on salesforce.com not trying to be the next Facebook or Twitter.
2010 will be all about revenue not unique visitors.