This is always a fascinating question to tackle, actually, because everyone has their own favorite dozen applications and add-ons, so I'll share mine, and then absolutely expect others to pipe up with their own selections.

Adium

As much as I wish I could just stick with something like iChat, the fact is that some of my friends and colleagues use Yahoo Instant Messenger, others use Microsoft's MSN service, and yet others, like my folks, are only accessible through AOL's AIM service. Then there's ICQ, once in a blue moon, and the .Mac service (which I think is AIM, actually). In any case, I don't want to have a half-dozen different apps running, and I certainly don't want dozens of different windows littering up my screen. That's where Adium is a winner. It's a multi-platform instant messenger application that lets me simultaneously work with AIM, YIM, MSN, and ICQ. Better yet, it's amazingly extensible, has a vast library of graphics and skins, and is tab-based, so when I'm talking to three or four people simultaneously, it's all happening in one neat window. get adium

BusinessCard Composer

If you've ever wanted to be a cool secret agent, able to produce cards showing you're part of the FBI, DHS, or Playboy Photographic Team, then this is the app for you. Even if you just want to do legitimate tasks, however, being able to create and edit your business card in BusinessCard Composer is fun, easy, and well worth the shareware cost. I find that I can continually refine what I say on my cards by simply printing 8-16 at a time and even sometimes having 2-3 different designs and asking people which they'd like. get businesscard composer

Firefox

Safari is a very good Web browser, but when I'm working on Web page design or just curious how a page will lay out in a different Web browser, Firefox comes to the rescue. It's extensible architecture also makes it a breeze to add any of the dozens of cool plug-ins too. get firefox

GraphicConverter

This might be already included on your Macintosh, actually, but if it isn't, download it today. It's a remarkably powerful graphics editor and viewer with support for more formats that you ever knew existed. I use it for organizing and viewing my digital photos, along with tweaking and editing other graphics and images. get graphicconverter

HTMLColorPickerX

If you're doing any work with Web sites at all, this color chooser is for you: it lets you instantly identify the hexidecimal rgb value for any color desired and can even constrain values to only that subset that's considered "Web Safe". get htmlcolorpickerx

MoreClocks

I have a dual monitor setup, and I really like to have a clock on each display. But I don't want the app visible in the Dock. That's where this simple freeware application proves a great winner. There are lots of different digital and analog clock faces included, and developer Luc Regnault is a pleasure to communicate with too, a nice bonus! get moreclocks

Norton Antivirus

Yes, it's a commercial application, and yes, Macs are far less susceptible to viruses than Windows systems, but if there's one thing that could cause me vast amounts of grief, it's a virus. And so, I pay for an annual subscription to Norton and have never had a problem in over a decade of use (and, yes, once or twice I have had it warn me of viruses). get norton antivirus

Palm Desktop

My Palm V has long since been relegated to the unused geek toy shelf, I admit, but darned if the free Palm Desktop calendar and contact manager isn't a superb, clean, simple piece of software that I use daily! If you're struggling to figure out how to manage your calendar and Mac's iCal doesn't appeal to you (well, that is, iCal + Address Book) then you might well find Palm Desktop a nice alternative. get palm desktop

PDF Browser Plugin

Talk about a brilliant application! This simple plug-in for Safari lets you view PDF files within your browser, rather than having to save them and launch a separate viewer. I've been enamored of this utility since I first bumped into it a few years ago, and can't imagine not having it on any of my Macintosh. Download it and install it. Then forget about it until you want to view a PDF! get pdf browser plugin

Saft

This add-on to Apple's Safari browser adds lots of interesting features, including lots of Address Bar shortcuts, but that's not why I have it loaded on my computer. Its winning capability is being able to save and restore all the active tabs and windows in Safari. Right now I have four tabs open in this browser window and a second window displayed on my second monitor. I can quit Safari, restart, and when I relaunch Safari, everything's instantly restored. get saft

Snapz Pro X

I take lots of screenshots and captures, and with Ambrosia Software's utility mainstay Snapz Pro X, I have complete control over what's captured, what format it's saved in, and what it's called. If you do anything with screenshots, this is a must-have utility. get snapz pro x

WeatherPop

This is a fun, somewhat goofy little application that adds an icon to your menubar that shows you a pictorial representation of your weather and the current reported temperature. Click on the icon and you'll get a seven-day weather forecast, from your favorite weather site. I'm not a weather nut (and I hate the ever-pessimistic The Weather Channel too) but this is a cool app, and being able to preset favorite locations is nice too: One mouse click and I can see the weather at my sister's house, my parents neighborhood, or my favorite spot in Hawai'i. get weatherpop

There are probably more applications that I use on my Mac quite a bit, including Microsoft Office, which includes my email app Entourage, which I use way more than I should, but that list will certainly get you started!