Neville admits it may be one of the most significant summers of recent years - and not just for United.
But he still expects the defending champions to raise their game.
"They should see it as a new challenge and an important challenge," said the England coach. "Since Sir Alex announced his retirement other clubs have already been lifted by the fact he is no longer around.
"The players should see that as a slight on them and say 'Hang on, do you think we can't go out on that pitch and perform without our manager?'
"That is a challenge in itself and ultimately the players and David Moyes will need to respond to that. It won't be a bed of roses - there will be ups and downs as there always is and there has been over the last 26 or so years.
"There will be pressure moments in the coming season when people will say 'it's not the same' but it's too easy to say that.
"Everybody is waiting to see how this post-Sir Alex Ferguson era is going to work. The club have had it before with Sir Matt but everyone here will stick together
"I think we will have one of the most interesting pre-seasons we've ever had and probably the most interesting start to a season that we'll have ever had: there will be new managers at three of the top clubs (United, City, Chelsea) as a minimum. A number of clubs will be wanting to start strongly: Manchester City, Chelsea, Arsenal - and Spurs will want to do everything they can to hold on to (Gareth) Bale and push forward themselves.
"I think United are in a good place. Do they get the credit they deserve? You only get that by repeating success - it's about winning, winning and winning again."