Only issue we had: with a 40 card deck, minus 8 cards per players' initial hands, leaves you 34 cards for drawing. This means one player will draw 18 cards and the other player only draws 16, leading to a possible situation where one player gets a whole extra turn than the other at the end of the game.
The canal period came out okay, because of removing the 2 extra cards, but the railroad period got weird at the end of the game.
Yes, my math was terrible. I was also missing that in the first turn, each player only does one action (probably Brass's most frequently missed rule?).
The other problem was that in a 2 player game, each player is pretty focused on their own world, so if the other player forgets to discard a card when taking a loan, shipping cotton, etc, (the ones which are easy to forget), it throws the whole total off.
My wife and I switched to a system where each player keeps the two played cards in front of him/her until the turn is over, which eliminated those mistakes.
Long story short: false alarm, move along. I was an idiot in multiple simultaneous ways.