We have been used to the fact that every second site looks like Twitter. That's because of their awesome Bootstrap UI framework. We've seen CSS frameworks before, but all of them were narrow enough to solve one problem at a time. Usually this meant a grid layout and resetting CSS. Twitter Bootstrap not only provides you with flexible responsive grids but adds many useful components. It's pretty easy to build a prototype site just by adding appropriate classes into your tags and see how beautiful CSS3 magic unfold on your pages.
From another point of view, a site built with Bootstrap loses it's individuality. When you see Twitter buttons and menus, you can even forget what site are you at. They generally look just the same. It's pretty ok, when you do a site for non-profitable organizations or an open-source project. Such sites will look clean and handy without a penny spent on designing them.
But how to make site look more unique?
Let's try something different then. There are many UI frameworks available. Most of them are free but some are commercial. Some can be great alternatives to Bootstrap and some are targeted for mobile usage. So here they are, with their official descriptions.
Foundation is the most advanced responsive front-end framework in the world. With Foundation you can quickly prototype and build sites or apps that work on any kind of device, with tons of included layout constructs (like a full responsive grid), elements and best practices.
Ultra–Lean HTML5, CSS, & JS Building Blocks for Rapid Website Production
Metro UI CSS allows to create a Web site in the style of Windows 8 quickly and without distractions on routine tasks.
Alloy is a UI framework built on top of YUI3 that provides a simple API for building high scalable applications.
As a conclusion, I'd suggest you to try Foundation if you are fan of semantic web and SASS. With 4th version of Foundation you can get rid of style-classes in layout and use only SASS mixins for styling. Groundwork was inspired by Foundation but adds something of their own. Try MetroUI or FlatUI if you prefer modern flat look promoted by Microsoft. If you want to have a site look like Jira, try Atlassian UI Pack. KendoUI and IgniteUI are the best for designing native-like mobile interfaces. Consider alternatives and choose the framework based on your tastes.