Well for one, it got rid of Growl support. Every Twitter app that I know of on the market has Growl support. No way to remove the menubar item. The new tweet sound gets annoying after you hear it millions of times. They even got rid of the HUD which I loved. And a whole host of other stuff I don't like about it. Twitterrific 4 feels like version 1 of an app, not a mature, 3 year old app.
But of course, I could use Twitterrific 3.