There is profit to be won on both sports, and people can use the odds in their favor to find an edge in either sport.
There are many more Premier League matches each season than NFL: the Premier League season is 38 games with 20 teams, while the NFL campaign is 16 games with 32 teams. In the NFL, there are usually the teams at the top that separate themselves, some decent squads, many teams that are average or below average, and then the teams at the bottom of the league. But with the point spread (the line on the game), it can be profitable to bet on the teams no matter where they are in the standings. The betting line is set to try to get equal action on both sides of the margin.
So there is an opportunity to win on each match.
The point spread in the NFL is much like the goal line spread in Premier League (or any football league ) matches. It gives the team that is the perceived underdog a chance to win you your bet.
With accumulators, the money line is usually the preferred way to bet. Money line bets can also work in your favor if you believe the underdog will win the game outright.