I've lived in Singapore for 6 years. I came over to work in a new company that some other foreigners (i.e. non-Singaporeans) that I knew had started. So we didn't have all the resources to ease the transition that the big companies throw at their people, like a moving coordinator to help with all the logistics of the move (find housing, get mobile phones, schools, etc). That said, Singapore is English-speaking and none of that is too difficult.
Unlike me, most of the Americans here seem to come on 2-3 year assignments with their companies, and I'm assuming you'd be coming on that kind of assignment. In those situations, the transition and the lifestyle are quite good since the company support is typically generous: large housing allowance, school fees, car allowance, etc. Singapore is very, very expensive these days in terms of those three things (housing, school (no realistic public school option), car), so make sure you understand what you are getting and that it's enough.
It's hard to answer a question about the "Singapore" work culture since it will vary a lot based on the company. There is a massive expat population here and a lot of companies won't necessarily have lots of (or a majority) of Singaporeans in its workforce. You may find yourself working with mostly other Americans or other Westerners. I think the largest group of "professional" expats are the Brits, followed by Aussies and then possibly Americans, but with lots of other European countries well represented and lots of Indian professionals here too.
Social life is the same everywhere: you'll end up making friends and socializing with the people you meet at work, through kids' schools and their activities (assuming you have kids), and possibly outside activities (such as a reasonably active running scene). My guess is that, due to the above, most Americans on assignment here mostly socialize with other Americans and a mix of other Westerners or Indians, but with some Singaporeans too if you know them from work. Singaporeans are generally not allowed to send their kids to the international schools, so your kids' friends won't be Singaporean and you typically won't therefore strike up friendships with Singaporean parents.
We came over when our kids were young and they've had good experiences at the international schools. One of my kids was young enough when we got here to go to a local preschool and that was good too. Singapore is not the suburban go-outside-and-play-in-the-street kind of place, but schools are good, crime is incredibly low, and weather is sunny (though humid). Kids are doing fine.
I wouldn't want to live here forever, but Singapore can be a nice destination for a 2-3 year assignment if that's what you are considering and assuming the company support is good. Good luck