An error as egregious as batting a weak hitting pitcher in the clean-up spot all season would result in a difference of about 16 runs over the course of the season or roughly 1.5 wins. Most moves that are discussed here, like whether Anthony should bat 1st or 3rd would result in a difference of about 2 runs over a full season, so they are relatively meaningless.
Who was the manager that talked about pulling his lineup out of a hat everyday? He would probably have about the same success as he would have if he constructed his lineup based on conventional wisdom.
I think you're right that it's more important to break up the lefties, and also more important to factor in a player's comfort level based on his hitting approach.
All that said, an optimal line up could result in between 5 and 15 extra runs over the season, maybe 1 or 2 wins, so in that sense, maybe not so meaningless. Sadly, managers typically don't go with the optimal lineup.