sitting on mines and shooting, and his level 2 is pretty damn effective.. not that the mines cant be bypassed or destroyed, but he has such a good strategy, and a good arsenal, and his supers are pretty affective for the amount of defensive tools and keep away game he has.
how do you grapple him when hes sitting on mines shooting though? plus he has an anti air grenade, and he can jump and lay more mines. im playing as him it feels kind of cheap. its not invincible but it feels cheap to melees lol. id imagine its not very effective against spike or jak though. its not like he feels locked down to one spot, because hes not too sluggish with ap gain, because of the ranged attacks. you can set up camp virtually anywhere.
most of the characters that are good against isaac are less played. i know radec is definately a decent fight for him, but characters overplayed like kratos and raiden suck #@# against him, which is good lol i like to promote non newbieness =P