Ok, so, having messed around a bit, I think I can confidently say that the manual fire actually improves the ISU's performance significantly. The ability to choose where and when to place your shells allows for far more consistent squad wipes. Plus, I now know precisely when I have another shot ready to go, which is a huge advantage in tank battles.
Well I honestly don't understand why people are so scared by lmg grenadiers. The base squad, the grenadiers, are so easilly killable. Yes, they have abilities, they can fight infantry, light vehicles and faust tanks but why are they so scarry? Lmg or not lmg equipped they are quite fragile and will disappear in a second if not carefully baby-sitted. Not the case of cons and rifles! Even if you are a bit careless you will still remain with 1 or 2 goofies in the squad that you can say "oh shit!" and quickly retreat when you finally see they are in trouble. Same thing with the volksgrenadiers. But poor grenadiers, they are the big loosers among main infantry squads.
Probably because they get the LMG upgrade relatively early and then absolutely shit out damage which causes squad wipes on the allied side if they stop paying attention for a moment. They really aren't that weak either - at least against other infantry (and, to be honest, with the way inf behaves in cover now, they really aren't that much weaker vs AoE either).