I'm not hysterical about Inquisitors, but they do make the game even at M/M a lot more challenging. I'm at turn 53 and am down to 3 generals, the rest of the lot having been torched. One of the living actually successfully led a crusade and has a 7 piety, and a second is hidden safely away in Ireland for the moment (though some heretics have sprung up in Scotland and corrupted several priests so that may change soon). The third is new and will likely die next turn. I get constant adoptions and Men of the Hour, none of whom survive more than a turn or two. Playing the game without many generals is hard, but it's doable (though seiges against cities that have 3 or 4 generals at the head of a full stack are pretty tough). My relations with the papacy are perfect, but the Inquisitors are left over from when the pope sent them against France. When I conquered France at the Pope's direction in the crusade, I inherited the Inquisition from them.

The irritating thing is that they ignore the heretics and witches and family members of excommunicated factions and go straight for my characters. Hard to do much roleplaying when you only survive a turn.

Assassins are useless; they can't even kill rebel captains in this game much less a Papal Assassin.