I try to build a first team squad of around 25 players, in such a way that I can have 2 first elevens. So I don't just pick the theoretical best 11 and then have a second 11.
I try to carefully balance the attributes in each 11, including not just their footballing stats, but also which languages they speak. I often buy Spanish and Portuguese speaking players, so find it better to keep them playing together where possible as it aids communication.
Although I try to get 2 fairly even first 11s, one team is usually a bit better than the other, so I usually use this team to play league games and the other 11 to play cup games, whilst occasionally using this team for league games when the other 11 is tired. I try not to switch players between the 2 teams, as I like them to get used to playing together. I would rather use the spare players in my squad as cover for injuries, bans etc.
I find that this works well for me as players are almost always above 95% fit when they play, they all get enough football so that I don't get too many complaints and each 11 plays together all the time, with as much language commonality as possible, so they gel really well.
Works for me.