1.) Twilight -- She'd be astounded by our technology and understanding of the universe without any assistance of magic. To ponies, magic is as fundamental as quantum physics here, so these basic differences in physics would be very interesting to both humans and ponies. She might also be concerned or even disgusted in how we use our more dangerous technologies and our enormous wealth to create a weapons of obscene and unthinkable destruction for the most dumb-shit reasons, let alone the more 'mundane' technologies that threaten our continued survival on this planet.

2.) Big Mac -- or any of the agriculture ponies, really -- would be astounded at our ability to create agriculture that feeds billions. Twilight would be interested, too, but she might also be concerned with existential threats to our food supply.

3.) They might be concerned of how human fillies and colts can end up killing themselves because of different pressures, usually over things that are less physical and permanent than cutie marks. I hope such pressures and dire outcomes are absent in pony society.

4.) Since Celestia has been wielding executive power for a 1000 years, Luna would make an interesting emmissary to the human world, to study it, and report back what she found. If she were the true princess of the night, she'd be enigmatic, quiet, and observant. She'd be the ambassador. Celestia would probably want a guarded relationship with all human nations.

In reality someone, say the US or China would pull something stupid and borish in the name of nationality and commerce, like going all Dutch East India Company, trying to establish a trading post somewhere too close for comfort, like what happened in Taiwan back in 17th century. Maybe start colonies and let them spread as far as the government could. That would be a mistake on that nation's part. Celestia would put the fear of the Pony Goddess Princess into them.

However, a hostile take over by humans is not inconceivable or maybe even difficult. The first obvious target would be to destabilize relations between the pony tribes. If this was the route we went, we'd have to find elements within the Equestrian head of the body politic. Perhaps selfish individuals with whom we could plot? Greedy merchant entities? The CIA has demonstrated a proficiency in using coups to overthrow democratic governments, such as in Syria-1949, Guatamala-1954, Brazil-1964, Ghana-1966, Chile-1973. There doesn't seem to be much of a military in Equestria, though. Even then, it might work out: there's no one to put up a counter-revolution; we'd just have to make sure we got most or all of the small military on our side. Alternatively, we could use our own forces. Hopefully our agents in Equestria could provide us with enough good intelligence to give us an edge.

Another CIA tactic would be to use agent provocateurs to pose as, say, communists, harass institutional leaders, intellectuals, teachers, etc. This method depends heavily on divisions in society that don't seem to be present in Equestria. We tried this with success in Iran-1953. The fighting started after we faked a sort of revolution to outside world. It's complicated.

All this seems unlikely, so the CIA would probably try to start some where else, putting pressure on Equestria. A direct military assault is something to remain reasonably agnostic about but as I mentioned before, a bad idea. So, with whom are Equestria's enemies? There are many inhabitants in the world where Equestria lives so it seems likely that we'd somehow ally with them. Some where, somehow, Celestria has enemies, trading partners, perhaps, whom desire Equestria's wealth. Rivals, etc. The dragons seem like an obvious candidate but we don't know enough about their motives. They certainly seem powerful but they're unable or unwilling to give Equestria much real military trouble; errant naps don't seem like a real emergency such as war, not if your first solution is to send a grad student and her 5 BFFs, and then have that plan actually work! We just don't know enough about the world outside of Equestria.

I imagine Celestia would recognize that not all humans are bad and that real benefit could come about from getting to know each other but she must also recognize that human institutions and culture can pose a very real threat.

If Celestia was smart, she'd tell us to GTFO. Ponies have created a better society than humans and they would have much to lose. We on the other hand are starting out at the bottom and have much to gain from them, and unfortunately, certain groups and select individuals would have much to exploit from them.

The one scenario I hadn't considered here was what if Ponies decided to invade earth? I can't imagine they would, though, since military domination just doesn't seem like how they roll. On the other hoof, compassion is a guiding principal in pony society and there's a chance that it could get out of control. What if it became like the relations between the old and new worlds and Celestia saw fit to spread ponydom else where?