This is an issue for 2D as much as it is for 3D. Setting a scale within your graphics program will give you much fewer (if any at all) headaches later when it comes to bringing things into Unity. Different programs use different measurements by default, so you will need to make sure that if you're using graphics programs such as Adobe Illustrator or Photoshop, your measurements are consistent – 3 mm is very different from 3 cm and 3 px.