To start things up I’ve been using the G5, this is a framework based on HTML5/CSS3 and  It has a bunch of useful must haves like CSS3PIE, Modernizr, a grid system, tool tips, image slider, lightbox modal box type, and other set of css defined classes to style text and forms elements.

From here I would start defning my layout with CSS and the grid system. If you’re not a grid user, please give it a shoot. Moving things around your site will become much much easier, I promise.
Also, from that list I really must recommend using Modernizr to detect when a browser supports a feature or not. Say you want to check if the browser supports rounded corners, you can drop in conditionals, and if the browser doesn’t support it, it will fallback to alternative solutions that you can define for older browsers.

if (!Modernizr.borderradius) { /* If it doesn't support the rounded corner */
	$.getScript("jquery.corner.js", function () {
		$("#some-div").corner();
	});
}

Cool article to get started: http://www.alistapart.com/articles/taking-advantage-of-html5-and-css3-with-modernizr/

To continue my app I define the application dynamic structure and flow using Backbone.js. This great library uses the MVC convention that will let you separate you application’s interface from the functionality. The maintenance of your code will become clean and easier to read. And you know how a javascript application can become bulky and messy after a few pages.

For the CSS I don’t think I have found anything better than LESS.  It enhances CSS with dynamic behavior such as variables, operations and functions.

http://lesscss.org/

And for the back-end I use CodeIgniter

Extras:

I also use a Javascript library called Kapi that let’s you define keyframed events to create anmations ala flash. Very cool.

https://github.com/jeremyckahn/kapi

And another fun library called spin.js. It’ll let you decorate and configure how your loader spin wheel looks based on a bunch of parameters offered on the site. Very handy.