Can Cycles use multiple UV layers? I'm trying to match Cycles to a Blender-Internal material setup and I didn't see a way for cycles to have an image reference more then one UV map.

Is it possible to have a node setup with 2 image textures, each using a different mesh UVLayer?
Yes, the different UVMaps can be selected by an attribute node and plugged into the vector input of an image texture node as well as into another image texture node vector input holding an alpha mask of the image referenced from the first texture node. This way multiple textures (and UVMaps) can be mixed for a single material output.

This technique is demonstrated in this tutorial.