Pitchers do lose effectiveness as the game wears on, I believe WIS has explicitly stated such. This is why relievers who get left out there for several innings (depending on their STA) get shelled a lot. Just think about it, if you threw your SP out there for a 245-pitch outing, he's probably not going to be striking out the side in the 9th is he?
My choice is to go with the #1 guy and turn his TPC/MPC down. I'd probably turn the Pull Rating up to 3, maybe 4 at the most.