I saw a significant decrease in my fps when I had the game in large screen, and I assume fullscreen would make it slower
lowest res + lowest graphics at fullscreen makes the pixels bigger and easier to render than at small screen
edmund said that for best fps always run fullscreen himself on his formspring :o
also beat isaac as cain and didnt take ANY dmg the entire fight :D
now i just have to beat him as eve and the chest here i come :D