The biggest change that you can actually play with is Reader. You'll notice that the "RSS" button in the address field changes to "Reader" when it's available. With a click, a new window slides up and displays the current article's reformatted text and images. It's printer-friendly, center-aligned and easy to read. From there, you can make the text larger or smaller, print the article or email it to a friend. It's similar to reading an article on the iPad with an app like Instapaper. Additional stuff on the page, like sidebar items, etc. is eliminated.
Actually, the email option didn't work for me. Instead of creating my message, Safari displayed a dialog box stating that I need to install Mail (it's installed). It's also kind of tricky to figure out when the Reader option will be presented. It won't work at http://tuaw.com, for example, but does for individual posts.
A smarter address field
Here's a welcome change, and something Firefox has done for a while. Safari 5 lets your search your history and bookmarks by URL, title or page. For instance, simply entering "Unofficial" in the field brought up TUAW. It's very handy for when you A.) Can't remember that great page you found but know that is was about B.) Are too lazy to bookmark things.
Just remember to use discretion when on a shared computer to save all parties some embarrassment, OK?
New tab behavior
It's as if Apple installed this feature just for me. As a long-time Firefox user, I've exercised the option to force all new windows to open in new tabs. I just can't stand new windows popping up all over the place. Yes, you could hold down the Command key on Safari 4.x, but who's got time for that?
Version 5 includes an option in the tabs preference to force all new windows to open in new tabs. Ahh, I feel better even typing that.
Bing is now an option for default search engine, just as it will be on iOS 4.
At long last, Apple has provided developers with a chance to write extensions for Safari. The door's wide open, folks, so have at it (Panic has head start).
The less obvious stuff
Not immediately visible is extended support for HTML5, an improved web inspector and hardware acceleration for Windows (it feels snapper on our Macs, too, but we haven't done any formal measuring).
All in all, a solid update for Apple's browser.