Unlock Mishra:
To unlock Mishra, beat Quest Mode using a preset duelist and deck.
Unlock Other Duellists:
Play arcade mode and beat it as each of the duelists; each time you win, you unlock the next highest duelist of that color. For example, win as Kuldan unlock Volita, then win as Volita to unlock Maraxus and win as Maraxus to be able to play Maraxus.