by codermike
I'd play with 3 heroes. The lower (H) score reduces the impact of the villain and is less to keep track of for the first game. Make one of the heroes Legacy. His support powers and one-shots will help a lot. The other two...pick heroes that look the coolest :) In my first solo game I had Wraith and Haka and that team utterly destroyed Baron Blade.It's worth looking in the manual for Complexity 1 heroes for the first game. Some of the heroes (like Absolute Zero and Bunker) really require you to understand how their deck works before you can play them effectively and that will be difficult if you're also learning how the basic game works.
I'd go up against Baron Blade for the first mission. Not that he's a walk in the park but he is more straight-forward. Omnitron is supposedly the same difficulty level but it ends up with a lot of things out and constant flipping makes it harder to keep track of. Citizen Dawn and Grand Warlord Voss are harder.
For environment I'd suggest Insula Primalis or Megalopolis. Baron Blade already has time pressure (before he flips) so you don't want the self-destruct of Wagner Mars base in there as well. And the Ruins of Atlantis are just plain mean :)
I'd recommend using the damage tokens as hit-point tokens instead. It's easier to look across the board and see who has 2 tokens left as opposed to trying to do math in your head for each target.
Avoid the Advanced Mode rules for the first game. According to the Sentinels Statistics Project it only makes the game about 10% harder but it's just another thing to keep track of. Speaking of, check out the Sentinels Statistics Project at https://docs.google.com/spreadsheet/ccc?key=0AqClP82b_XgZdGJ...
As soon as you finish you'll want to play again any way. This is a great solo game. In fact, it's the only way I've ever played! Have fun and let us know how you did.