I'll speak from experience here. I used to be a starter and, to be honest, I had better success the shorter the break between innings was. If you are pitching well and you are in the rhythm of the game, you want the ball in your hand every pitch. I almost wish I could pitch my seven innings, let the opponents compile their runs, and then let my hitters hit for seven straight innings. That said, it is always re-assuring when your team puts up runs and it allows you to relax more on the mound. I found I made less mistake pitches when pitching with a comfortable lead than I did in close games where I was pressing with accuracy or velocity.
For the most part the same is true in the major leagues, except to a lesser extent. I know that in many rain delays, a starter will be removed due to fatigue even though he may have only thrown 50 pitches. I can see why a pitcher may become fatigued, but when you have played baseball for as long as major leaguers have, I'm sure they are plenty used to it.