When I do sandbox, I craft the setting with a lot of level-appropriateness built in. Imaro seems to be saying that in his sandbox, if its written that the Emo Caves are full of lvl 2 goblin cutters, then that's set in stone. If the PCs visit the caves at 1st level or 10th level, that's what they find.
I don't generally set up my sandbox like that. Sure, the home of the lich sending forth legions of undead to harry the common folk is going to be a very powerful locale, one that doesn't change much. If the PCs go there at 2nd level, they would likely die. Same for trying to challenge the great dragon that lives at the other end of the valley. Maybe they get ambitious and try to steal from its hoard, though.
But many of the locations aren't built with set in stone mechanical numbers in mind, and those numbers are certainly not required. Why do the Emo Caves have to have lvl 2 goblins? Why not lvl 4 or 6 goblins, depending on when the PCs go there. Or some tough bugbears and hobgoblins? This is where level appropriate design fits. Many of the locales I design, I write notes about the story of the place, hooks as to why the PCs would seek it out (treasures, rumors, whatever), and notes on what monsterous challenges are faced there depending on what level the PCs visit that locale, within a reasonable range that makes sense, of course. If the PCs seek out a tribe of Forest Giants at 1st level, they aren't going to find weak, lvl 2 giant kids everywhere. (Although, a lord of the flies variation done with giant kids could be crazy...idea file) But I will have notes on that giant tribe on how to modify the challenges based on when the PCs visit. The numbers of the system are meant to gel in a game that works.
The Tower of the Mad Wizard? Well Archie is mad, and a major league NPC regardless, but I don't have to have stats set in stone. If the PCs become involved in his shenanigans, its needs to be a challenge when they go after him once and for all. The Caves of Despair? Well there are things that can cause despair to 1st level nubblets and 18th level badasses. Where the monstrous humanoids live? There are enough types of monstrous humanoids, that I can fit about any level of play in such a locale.
Now, I've done sandbox this way for years, but I love the ease of which 4e adjusts to this style of sandbox game. Memorize two short formulas (+/-1 AC, defenses, attacks / lvl; +1 damage / 2lvls) and the location of the hp by role table and you can easily adjust monsters in a location on the fly by +/- 5 levels. So if the PCs tackle the troll warrens at 6th level, drop the basic troll by a couple levels and take out the wartroll chieftan. If they go there "late" at mid paragon, level up the basic trolls, use more wartrolls and make the chieftan a felltroll. Those are all just numbers to provide the challenge to the game, they are really irrelevant in the scheme of things. The locale didn't change, the PCs make their choices, a good challenge was had by all.