It depends on how you typically use CSS to set up your pages. They wind up using less semantic classes ("indent-12" vs. "rail-content") if that's important to you, but they also solve a lot of layout issues people tend to run into.
They take care of the need (mostly) for floats, which can break designs faster than... well, something fast.
What they make harder, however, is customization. If you don't take the time to learn just what those classes mean, it can be hard to make things look just the way you want because your CSS rules might clash with something you didn't know about.
They are great as a way to switch from tables to CSS-based design, and they also really help implement the "grid" theory of design, where things line up and are in horizontal and vertical rhythm.
Take 'em or leave 'em (I left them, but sure played with them a bit)
EDIT: I used both 960 and blueprint, about 8 months ago or so. Unclear if significant changes have taken place since then.