We played an Easy Mode game with the Virulent Strain, then switched to Normal Mode (5 epidemics) for a few more games with the Virulent Strain and one with the Mutation Challenge (but not with both).
Overall, it doesn't seem like the OtB additions have an enormous effect on the 2 player game. Maybe it was just lucky draws, but the only time the Virulent Strain ended up having a significant effect on us was when I was playing the Dispatcher (can move other pawns around) and she was playing the role that auto-removes a cube from a city with 2+ cubes, and we drew the effect that you can't leave a virulent city without using an action to Treat it. So I couldn't move her pawn through certain cities anymore.
In the one game we played with the Mutation Challenge, we did lose, but the purple cubes had very little to do with it. There was never a point where purple cubes spread out organically, only popping onto the table from card plays.
The point at which we lost the game (which was the case in most of our games) still does feel a little bit anticlimactic. But what can you really do about that? You have to go into this game understanding that the game just stops at a certain point.
I don't count that as a huge negative, but it is a change from other games.
Another minor negative is game setup time. Whenever you start or restart the game, you have to pull out a whole bunch of cards from the player deck, sometimes pull out cards from the infection deck, reshuffle things, deal cards out, and then reshuffle one or two more times. That can get more shuffletastically annoying than Dominion, and I'm thinking maybe I will have to sleeve the Pandemic cards after all.
I'd love to give the game more of a chance, especially trying it out with more than 2 players. And the Bioterrorist looks like a spicy little variant too.
I definitely rate it at least a GRRR.