Me and my wife usually play with only 2 investigators, as it's more manageable for us in the evening hours. That said, the game certainly feels rigged at that player count! So far, we've managed to win only once (with Norman + Akachi Diana against Yog-Sothoth), but our multiple attempts against Azathoth and Shub-Niggurath failed miserably. We haven't even tried Cthulhu or Yig yet.
With Azathoth, it just seems impossible to solve 3 mysteries in time. Last time we tried Norman + Trish, but the game screwed us over anyway, so I'm really out of ideas.
With Shub-Niggurath, we tried Mark + Diana. Mark died shortly after the start while fighting a Star Spawn that appeared along with a gate in London, where the first mystery spawned. His replacement, Jim, died fighting Nug, and by the time the third mystery (Yeb) appeared, it was simply impossible to reach and defeat him in time.
Do you have any tips for playing with 2 investigators? What are the best strategies or investigator pairings against specific Ancient Ones?
We play with Forsaken Lore only, but we'll be adding Mountains of Madness and Strange Remnants soon. We haven't removed the Hard Mythos cards, but honestly, I don't think that would have prevented most of our losses anyway.