im not sure of your ability level so forgive me if you feel like im talking at you like your just starting out if thats not the case...but the key is rotation. So for that russian league/BPL hybrid i have McGeady at LM and Hulk at RM. Then on the bench i have Tosic who is a LM. This way i can use the three of them to rotate through. One game will be McGeady at LM and Hulk at RM, then the next will be Tosic at LM and McGeady at RM, and so forth. This way you only need one sub. Then i do the same with the strikers. I have Emenike on the bench and do a little rotation with Eto'o, Welliton, and Emenike.
Unfortunetly you can't do this with CAMs and CDMs in 4-1-2-1-2 but depending on what formation you're using could work. With this system i have had to buy only 4 extra players to keep everyones fitness up.
As for the Defense tho, it's hard to find good D that has the specific attributes i need (CB's are french and in BPL, RB is Brazilian (for chem with Hulk) and BPL, etc.) so i just use fitness cards for them every so often.