The schedule always matters. Winning on the road and beating quality opponents is harder. The good and great teams just do it a lot more.
Sure. 500 is what you'd like to see whether after 40 games or 60 games. But I'm prepared right now to say there's no way they're going to be 20-20, and that's due to the schedule as much as anything.
They are 5-10. Best case they come home 8-11 (which would required a win today and a series win in Chicago). And then win three of four at home against Colorado to hit 11-12. I reckon they go 8-11 from there (between home series against Seattle and the two road trips). That would be 19-23.
Maybe they do better than that and hit your mark at 21-21, but they could also be be 15-27. Like you say, right now they can lose to anyone, including possibly today and in Chicago.
The good news is if they do get their act together after that, sure, they will be fine. But possibly out of the division already, just like last year. The only plus is there won't have been any head-to-head games yet.
And sure, maybe they'll go to Houston, be inspired by the Series rematch, and sweep 'em, and do the same at the Dodger Stadium (where they even won last year with Girardi).