As much as I love Apple's cleanly-designed Safari, it's just not quite up to snuff for me anymore. I've taken to using Gmail to manage all my email activity -- easier to check on the road, seamless handling of multiple accounts (I have at least 4), and a near-total elimination of spam. Google sends Safari a slightly dumbed-down version of Gmail due to that browser's poopy JavaScript performance, so with mixed emotions, I defaulted over to Firefox RC2, moved my bookmarks over, and that was that. Firefox 2 has fixed a lot of the things that I used to dislike it for: clunky-looking fonts, ugly browser chrome... I think Firefox used to be a clear product of an engineering-driven effort: great standards-compliance, performance and security, but not much in the way of consumer fluffiness. I think it's mostly overcome that.
There are still a few things I miss about Safari, particularly its integration with the OS (such as dragging an image out of the browser, onto the dock and into Photoshop), but I can work around those issues. Firefox's overall performance is a lot faster.
In addition to Gmail, I've started using a few other web-based apps in my daily routine: Harvest to track my hours, and Blinksale to manage all my invoicing. Like many professional service-oriented industries (design, law, etc), everything revolves around the hourly rate and tracking and reporting one's hours is essential. I've seen all kinds of methods, and Harvest blows them all away. Super clean and easy. It's nicely designed on many levels, and if I were still working at an agency, I would encourage them to use the enterprise level of the app.
On the billing end, Blinksale does what it's supposed to do, although I really wish that Harvest would build a billing interface into its system (I'd pay more for it), which I believe would make it the killer app for freelancers and contractors such as myself.