Casting Conflagrate with my opponent having a Spellskite on the battlefieldSpellskite on the battlefield and I cast Conflagrate for its flashback cost dealing a total of 7 damage. I choose to target a Birds of Paradise (1 damage), Noble Hierarch (1 damage), and the other five to my opponent's face. Since Conflagrate says "any number of target creatures and/or players," will my opponent have to pay 2 life per 1 damage? Or if they pay it once, all damage from Conflagrate has to go to Spellskite?
The way you described casting Conflagrate it has 3 targets. Spellskite can change any one of those targets to itself, but can only be a target for the spell once. Presumably they'd spend 2 life to change the target from themselves to the Spellskite causing Conflagrate to kill 3 creatures. If you instead chose to deal 1 damage to Birds of Paradise, 1 damage to Noble Hierarch, 1 damage to Spellskite, and 4 damage to their face, they would not be able to use Spellskite to change any target of the spell.