I've used hand markups scanned in, PDF Converter from Nuance, Adobe Acrobat and PTC's ProductView. While hand markups are the most versatile, color scanners make large PDF files, non-color scanners can make your markup hard to follow. Adobe's and Nuance's product are similar, so I switched to the less expensive Nuance software and I don't miss anything that isn't available with it. ProductView is great for simple markups and since the markups are automatically linked to the object, very direct. However, it lacks the markup tools found in the two PDF products.
I have also tried Imaging by Global360 (previously Kodak) and it is excellent for markups in Jpeg and Tiff. The files are small, and you don't need special software to view them (Windows support both file types). The rubber stamp annotation is far superior to the PDF, and it has the ability to directly make annontations part of the file. It cannot, however, protect the file outside of filesystem protections.
