Sprites will lose quality if you scale down, there isn't any way around that. If you scale down by 50%, you're displaying 1 pixel for every 4 pixels, so you've lost 3 pixels of data...Scaling up on the other hand will just either make the sprites more blurrier when scaled up (though should look similar as you're displaying at higher resolution), or more pixelated.
Alternatively, if you don't want to scale, and just want to display more information (like Terraria for instance), then you won't loose any quality that way.
If you want to scale, I strongly suggest working at the lowest resolution you'd like to support, and then have a double resolution version you switch to when the resolution is sufficiently high that you start to notice the lack of resolution - or have it as an option somewhere in the game (Sprite/Texture Quality).
As you can imagine, all of this (and how you set up the system for it) really depends on the kind of game you want to make and how you want to display your sprites. I need more info to be able to suggest anything.