Estimates of the number of users running with JS disabled range from 10% to 25%. That can be a significant number for a commercial site, so you may end up turning business away if you require JS for functionality. There are also issues with accessibility, as JS can interfere with screen readers and other adaptive technologies.
With the advent of "Web 2.0", more sites are requiring JS to deliver core functionality in their pages. The trade-off is a reduced audience for a slicker presentation. You must decide which bests serves your purposes.
In terms of search engine ranking, I doubt you have much to be concerned about. In terms of site usability, well, that depends.