A strong case can be made for the first run of the game.  At the start of a game, each team has a 50-50 chance of winning (in general).   The team that scores the first run ups their chances of winning to about 65%.  That's an improvement of 15 percentage points.
 
However, looking at the American League this year, the real answer is the fifth run.  Here are the records in all AL games this year when a team scores four or five runs:
 

Runs Scored	Record	Winning Percentage
4 runs	81-103	.440
5 runs	120-69	.635

 
The increase from a .440 winning percentage to .635 is huge!  In fact, this increase of 19.5 percentage points is the largest of all the runs scored comparisons.  And it's larger than the value of the first run.
 
The two teams with the best records in baseball scoring five runs?  The surprising Washington Nationals (12-2) and the first place Chicago White Sox (17-3).  The White Sox reeled off 17 in a row between losing their first game and their last two games with five runs this year.