The in-game rest settings are a two part function. First, the setting you have on the rest portion of the "Team Managerial Style" will dictate whether or not rest is used. If you uncheck the boxes for "Rest players if winning/losing by X or more runs in the X inning or later", then no players will ever rest. If you do check this option, then it will allow for players to automatically be rested if winning/losing by whatever margin you set.
The other in-game rest setting are the "autorest" settings found in the "Advanced Settings" area, and involve the "Allow Rest" checkbox (check for yes, uncheck for no) and the percentage next to their name. If you do allow rest, and the player/pitcher is below this number prior to the game starting, then Sparky will automatically rest them until they recover above this number.
All position player rest settings can be set in the "Player Hierarchies" popup. The thing to know about this is that at each position, the player you have listed to the furthest left will be the first player Sparky checks to see if available for rest. If you put your starter furthest left, they will not be taken out of the game for resting purposes even if your backups are listed next. You must order each position left to right by which player you would want to come into the game first for resting.
Hope it helps...