CMYK or RGB

It simply depends where your layout is going to end up: on Paper? on Photographic Paper? Web Site? Screen/Projector presentation?

CMYK color mode employes Cyan, Magenta, Yellow and Black ink to produce the image. This color mode is commonly used in traditional printing industry and new era digital printers. Your desktop printer most likely is CMYK based as well as your laser, copier and and large format ink-jet. If your layout ends up on one of these devices your workflow has to be set up with CMYK profiles. You may have some RGB profiles included (for your scanner and monitor) but at the end you'll see and get CMYK color.