IP/G affects in-game fatigue. You can use a pitcher in a LIVE game to see exactly how his fatigue % goes down as his pitch count goes up. How far you want to push in-game fatigue is up to you. Most people would use 15-16 pitches per inning as the guideline for determining a guy's pitch count based on his IP/G.
For example, if the IP/G is 7, most owners would set the pitch count around 105-110. If the pitcher is throwing more pitches than that in a single game, he'll get more tired and may allow more hits/walks/HBP/wild pitches/XBH, etc. at the end of his appearance, when fatigue is lowest and performance will suffer most.
An SP used as a reliever should not see any drop-off in performance for that reason alone. It's why you see so many Milacki, McQuillan, Carlos types with outstanding relief seasons in the SIM, and why some owners with extra starting IP will allow starters to be used as relievers as well.