I use Twhirl as my Twitter client. I love it. The only problem I found was it’s insistence that links be opened in IE instead of my default Firefox browser. Well, turns out it’s not a Twhirl problem it’s an obscure Vista setting. (Non-Vista users have not had this problem.) So, if this is happening to you here’s the solution with screenshots. (Originally from twhirl’s blog.)
First close Twirl if its running and open up the control panel, switch to classic mode if you haven’t already and select "Default Programs".
Next, select "Set Program access and computer defaults". (You may need admin access for this.)
Lastly, expand the "Custom" group and under "Choose a default Web browser" select Mozilla Firefox.
Click OK and get yourself back to the desktop. When I started Twhirl my links now opened in Firefox.