Like I said, I always make at least one sub, and it depends on the score and the opponent.
It is hard to advise someone on this as there a many variables to consider.
if it is not for fresh legs, usually one subs to change the game, either by a change in formation or personnel. With this game engine it is hard to determine if subs actually do anything, because as I have previously mentioned, this game might pre-determine scores, which means that all in-game action made by the manager has no effect other than to change the useless possession bar and the in-game commentary.
With subs, its always would have, could have, should have if you lose or tie, but a masterstroke if you win. Example: If Chelsea had subbed Terry during the CL final vs ManUre, they might not have lost in a shootout (what sucks is that I hate both teams, and wanted lightning to strike them all down, but I hate Chelski less and wanted them to win.
)
Anyways, in other games I dont watch for whatever reason, I still win against people who make subs, so it all depends on the situation.