Okay, so I got rather bored and decided to calculate the number of possible game configurations playable with the current sets, up to and including Shattered Timelines. So, we're working with 18 heroes (plus 13 promos [including two alternate Legacies and two alternate Wraiths]), 20 villains (18 normals and alternate villain cards for Baron Blade and Omnitron) and 12 environments. We'll assume that we can have any number of players, Normal or Advanced mode, and no duplicate heroes, even if the promos represent different individuals.
Environments are easy: there are 12. Villains are only slightly harder; 20 villians x 2 difficulty settings = 40 configurations. Multiply that by 12, and you get 480 - the number of villain-environment combos.
Heroes are somewhat more difficult. I'll start with five-hero games, so that I can get the most difficult part done first. Assuming no promo heroes, there are 18C5 combinations, which = 18 x 17 x 16 x 15 x 14/5 x 4 x 3 x 2 x 1 = 8568. With one promo, you have 13 x 17C4 combinations, which = 30940. Two promos is 13C2 x 16C3 = 43680, three promos is 13C3 x 15C2 = 30030, four promos is 13C4 x 14 = 10010 and five promos is 13C5 = 1287.
The problem with these figures is that they will include setups with both promo Legacies or both promo Wraiths. So we need to subtract the following number of setups: 2 x 16C3 = 1120 (two promos), 2 x 11 x 15C2 = 2310 (three promos), 2 x 11C2 x 14 = 1540 (four promos), 2 x 11C3 = 330 (five promos). And we're still not done, because with that we'll have removed any setups that contain both Legacies AND both Wraiths twice... So, add back on 14 and 9. Total those figures and you get... 119238.
Okay, so now for the four-hero setup: 18C4 + 13 x 17C3 + 13C2 x 16C2 + 13C3 x 15 + 13C4 - 2 x 16C2 - 2 x 11 x 15 - 2 x 11C2 + 1 = 25586, and three heroes: 18C3 + 13 x 17C2 + 13C2 x 16 + 13C3 - 2 x 16 - 2 x 11 = 4064. So, 480(119238 + 25586 +4064) = 71,466,240 possible configurations.
That's a lot of setups.