The main difference is a percentage of a color accounts for a white under base, and transparency is with no base.
In this example, the colors on the left are 50% fill, and the colors on the right are 50% transparency
They can print the same on press depending on how you setup your under base and artwork.
I prefer the transparency route, as if you stick colors underneath it effects the output more realistically on press, but it really just depends on how you setup your art, as to the rip the whole image will output a 50% black halftone across the image, the rip doesn't see a difference (unless colors are overlapping, and even then you can hit overprint and then the percentage is what you set the transparency.)