Both resist transmutation, one hit kill and death hax, so let´s just leave those at a side.
Mario has some hax Isaac doesn´t resist, like Time manip and Sleep manip, but I´m sure Mario doesn´t lead with them, but can flip the match to Mario´s side if used right.
Now, Isaac resists a bunch of sorts of elemental attacks, leaving most of Mario´s ranged attacks hardly useful, however, his Blaster can help to restrain Isaac by covering him in honey and/or ink, which can give the match even more to Mario´s side.
What Isaac has at his side? Far better ranged attacks overall, a good variety of moves that allow him to attack Mario across all directions can give Mario trouble, but the Cape Feather and the Hammer allow him to reflect some of them back.
He also has this move that sounds broken:
"Bind: Isaac seals the usage of the opponent's spiritual, mental, physical, magical, psychic, and elemental abilities."
Mario also has Cappy, which can allow him to win the match quickly via incap, but so can Isaac likely win quickly with Bind, so I go by inconclusive TBH for now.
