I'm seeing a lot of juxtaposition in the trailer. It starts out making Los Santos to be this idyllic, glamourous place, but as it goes on, the city looks like it's about to be swallowed up in squalor; there's the guy whose bank foreclosed on his house, and frequent shots of the city's homeless. At the same time, we've got private jets and luxury cars zipping around, and all these symbols of wealth. So the economy is clearly going to be a big part of the game, and I think the theme will be "What drives a person to commit crimes?". With the economic factors in mind, I certainly think we're going to be sympathising with characters who resort to robberies out of pure desperation.
If I may extrapolate from that, I would not be surprised if GTA 5 breaks with tradition and starts with a character who is not a criminal. The voice-over keeps talking about getting out of the business and starting over, but I think he could be something like a banker who a lot of people blamed for foreclosures in the city he originally lived in. Unable to take it anymore, he decided to get out of town and moves his family to Los Santos, using what money he has to try and buy his children a future. I think it would be pleasantly ironic if the protagonist never actually commits a crime until he arrives in Los Santos. The risk of all this is that the game would get too preachy.