With prospects, the regular season games are no more meaningful than ST games, unless you really care about that AA World Series trophy. So no need to worry about a guy getting hurt in ST and missing out on all that hot minor league action. As Mike points out, your player will have a lot more time to recover from an injury in ST than late in the season. So go ahead and play the prospects.
If you're worried about injury risk (albeit a low one), It makes some sense to rest your fully developed Major League guys, though, since they eventually are going to play games that matter. Well, as much as anything in HBD can matter, that is.