Playing a couple dozen games would probably answer many of your questions.
Here is a basic primer and not meant to be comprehensive or strategic in nature.
Hero modes: Initially hit selected hero 2 times to start except Wolverine which is 4. Finish mode by returning to the hero and/or hit other lit shot(s) as directed by playfield.
Yes, Villains have health meters. Shoot lit shots as directed by playfield and DMD.
Some Villains stack better with multiballs, others are easier to complete in solo play.
Brotherhood and Hellfire are multiballs
In Wolverine, hit a flashing shot, then Wolverine.
Enjoy!