In your opinion, using the spell Bones of the Earth, can I target a Huge or larger creature with more than 1 pillar?

you can target ground under a creature if that creature is Medium or smaller.

It seems RAW it cannot. Generally if it specifies when you can do something, other situations you cannot. As a house rule it would probably be fine. I would probably give advantage on the dex save if you didn't cover at least half of the creatures space with pillars though. Also I probably wouldn't add damage per pillar against a target.

I completely skipped that sentence.. So yeah, the answer is no.

While technically RAW you couldn't, I would house rule it and say that if you target four of the pillars under a large creature it would act as one large pillar. Still only 6d6 damage, and no other bonus for having multiple pillars under the creature other than the ability to do it. It just doesn't make sense to me that you can't do it if you cast four pillars under the same target. Well unless the idea is that a large creature blocks your view of the squares under it thus you couldn't target them. 

It is a nice idea. 

I'd probably allow it as well just for fun and the cost of more pillars, but the reason it isn't allowed in RAW is likely because of the creature's weight. A Huge creature is at least three times the weight of a Large one, so even with more pillars, it may just not be possible to lift it in the air with rock pillars.

In the theoretical situation of a very sturdy ceiling:

What about 1 Pillar under a target, and another pillar under the same target...6 times? dealing 6d6 damage 6 times. because surely you still have ground in a 5ft square beneath a medium or smaller creature, and surely the pillar would once again be prevented from completing its full height and so surely it would deal it's damage again?

an underground cavern with a height of less than 30 feet would likely be ideal?

Quote from Kroeger29 >>

In the theoretical situation of a very sturdy ceiling:

What about 1 Pillar under a target, and another pillar under the same target...6 times? dealing 6d6 damage 6 times. because surely you still have ground in a 5ft square beneath a medium or smaller creature, and surely the pillar would once again be prevented from completing its full height and so surely it would deal it's damage again?

an underground cavern with a height of less than 30 feet would likely be ideal?

 
No. The creature would be on the pillar, not on the ground, so can no longer be targeted after the first pillar. And since the space below the pillar is no longer ground anymore (it's now pillar) it cannot be targeted again.

As a homebrew rule I'd allow you to combine multiple pillars into one extra long pillar - but the effect on a creature would be exactly the same - no extra damage, simply because it would not cause more damage in the real world either, but now you can use it for higher ceilings.

Will also note this spell isn't really designed as a "damage" spell. The focus is creating pillars for utility purposes like helping you reach higher ledges, provide stability to a roof, or when being combined with Wall of Stone to literally create buildings.

If your intention is damage or restraint you have superior, and lower-level, options available to you.