It's having players and managers who are used to that 2 game a week grind as the travel means you have limited time to train on tactics during the season as it's basically play a game 2 days recovery sessions, 1 tactical session then game again and it's basically that on repeat all season.
I know a few Wolves fans and they were saying this season they're nowhere near as good because the team is shattered as they haven't rotated that much in Europe but they don't play a particularly draining style whereas Sheff Utd are surprisingly front foot for a defensive team they don't just sit back and absorb pressure. The Wolves fan was saying until they played us in the league when they'd finally had a rest after about 60 minutes in every game they were dead.
Think part of our problem is the two seasons of Europa League football we've had from the start we also got through in the league cup to the semi finals. Think in his first season under Mourinho we had some ridiculous spell where we only had one week between Xmas and the end of the season where we didn't have a midweek game (apart from international breaks). That side was dead by the end of the season they were dropping like flies every game as we just had to patch players up and get them back out on the pitch.