A reputation for honesty is your most important asset
If you want to make deals, have a reputation for keeping your word before you show up to a negotiation. It matters more in industries with very few players since you’ll have to keep working with them or take them out.
Work smarter, not harder
The Wire shows there’s a huge negative correlation with hard work, risk, and reward. Those on the street-level, including the police, were exposed to danger everyday with low pay and marginal opportunities for advancement. The top brass could sit around and play games while their people made money for them. Further, it took smart moves, not hard working for the cops to make busts.
Life is beyond your control, manipulate it anyway
The show does an excellent job of showing many competing forces clashing against one another. The rival gangs, the police, the city, the media, and so on. No one can control the future, but a donation here, a favour there... add in some allegiances and you might have some serious influence.
You find able people by testing them
Do you think Stringer Bell handed Avon his resume looking for a job in the gang? No one gets a high-level job in a gang without earning it. Before putting someone on the payroll, test their abilities and allegiance (or perhaps sense of purpose).
You can’t be too organized
There’s a reason they call it organized crime. In season one we see the professionalism and attention to detail of the Barksdale gang avoiding the wiretap. In season two meanwhile the sloppy disorganized working class port criminals can't help but get themselves exposed. If you want a fluid, fast paced organization, prioritize details. Sweat the small stuff.
Play the long game
An empire isn’t built overnight. If you want to win big you need to invest in your future success by building relationships, preparing contingency plans, and planning an exit strategy. Don’t cause a splash and catch the eye of competitors, just slowly build and reinforce your organization until it’s too late for the opposition to stop you.
I could be wrong about my interpretations from the show, but I’m not wrong in thinking it is one of the greatest shows to ever run.