I use DreamWeaver, and it automatically determines "safe" areas for you, depending on your target monitor setting. As for what's a good target monitor setting to choose, 800x600 is the best general bet, but you could go to 1024x768 if your target demographic is sufficiently high-end to justify it.

BTW, if you want to break the mold without breaking any browsers, consider going horizontal, like this:
http://www.themicrofoundry.com
The height is determined to fit in a 800x600 display (while allowing 640x480 users to scroll down once, and then scroll only horizontally, with the [low-relevance] "header" cropped), and the widths were determined to the pixel to provide nice even jumps of the scroll bar in virtually any browser without little bits left at the end. Actually, this was only true until about a year ago... I've gotta update my widths for current browsers. :-/

hhp

For a good general reference on creating a web site check out http://www.webmonkey.com where they have a wide variety of articles, tips and tutorials to help you out.

Head straight for the Quick Reference section and the How To Library on the right of the page. Of special note is their Browser Chart which I've used many times as a reference (which at last check pretty much echoes the 600x800 spec Hrant gives above).

The writing style is light hearted without dumbing down the info and they don't bog you down with too much text ~ just enough to get your feet wet in the subject at hand.

Besides the Monkey, I also recommend http://www.designinteract.com for further articles on the design of web sites. In particular, I found their Site of the Week useful for good concise reviews of a wide variety of sites.

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ImageReady is the better program for creating web sites and graphics. Although PhotoShop will work, IR has more webcentric features (BTW ~ is anybody else out there waiting for the day when Adobe will simply merge the two programs and make our lives that much easier?)

Adobe's products (of course) work best with their own web solution, GoLive. However, I prefer DreamWeaver. It's a very robust program and has a lot of helps for setting up a page for the target audience (as Hrant mentioned above). Perhaps best of all is their try before you buy 30 day trial version you can download from their site. As my DreamWeaver teacher told me, "if you can create it in 30 days, you can do it for free!"

Other things to think about besides screen resolution is the speed of the target audience's internet connection. Are they on a modem? Cable? DSL? And the platform ~ Mac? PC? Linux? Palm? Cell phone?(ugh!)

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Hrant's suggestion of a horizontal scrolling web site is a great way to try something different, but be careful ~ it's easy to let novelty get in the way of functionality. If you want to try it, study Hrant's and see why it works.

I would strongly recommend learning the nuts and bolts of HTML. While my tools, like Hrant and Roballoo, are ImageReady and Dreamweaver, DW will occasionally not do what you want it to do, in which case you'll need to go into the HTML and see what's going wrong. I personally like Peachpit Press books, though I don't know their current lineup of HTML books. But I'd look at them first and see whether you like their style.

Being a print designer first, I had a hard time working at 100%, meaning that I have to refrain from zooming into the artwork/layout because it doesn't really affect it. Always, always work at 100% (command-alt-0) what you see is what you get. Another print habit that I have is zooming out so I can see the overall layout, I also squint my eyes very professionally. If you zoom out it looks like •••• *, so don't zoom out.

I always use ImageReady, Photoshop tends to alter the color when saving for web (I'm serious.) I also enjoy Dreamweaver profusely, whatever it can't do I simply hand code it. If it is easier for you to learn software programs than programming languages (HTML) I'd say start with some tutorials on DW and you will slowly learn and understand what the HTML is doing.

* What the hell? Is there no cursing on this site? ••••, ••••, •••••••... nope, there isn't. Cool.