I don't play the game anymore, but as others have said, (unless things have drastically changed in this regard) I think it pretty much completely depends on which plays you like to run and which direction you run them.
Back when I did play, I almost exclusively ran to the left (mostly because I wanted to have maximum field to throw to the right), so my best blocking WR went to WR2. But that doesn't necessarily make it the right setup for everyone else.
I don't play the game anymore, but as others have said, (unless things have drastically changed in this regard) I think it pretty much completely depends on which plays you like to run and which direction you run them.
Back when I did play, I almost exclusively ran to the left (mostly because I wanted to have maximum field to throw to the right), so my best blocking WR went to WR2. But that doesn't necessarily make it the right setup for everyone else.