Methods and systems for generating a reference image for use in a process performed for a specimen are provided. One system includes a virtual system configured to receive output generated by actual systems for specimens, each of which has device areas of the same type formed thereon. The virtual system is configured for identifying defective portions of the device areas based on the output generated for the specimens by at least two of the actual systems and eliminating the defective portions of the device areas from the device areas in which the defective portions were identified to thereby generate remaining portions of the device areas. In addition, the virtual system is configured for generating a reference image from the output generated for the remaining portions of at least one device area on a first of the specimens and at least one device area on a second of the specimens.