Marked for Death and the Valley of Death Rune
Valley of Death transforms Marked for Death from a single target to an area-of-effect on the ground. When you target a mob with the skill with the Valley of Death rune, it's just dropping the AoE at their location. This is no different than using the skill on an empty area. This means that there is no target for Marked For Death to receive the initial +15% damage modifier and any mobs under your cursor only get the debuff from the AoE on the ground.