Here is a good basic description of how the “46” lines everyone up, courtesy of Wikipedia:
Defensive ends: The weak side defensive end lines up one to two yards outside the weak offensive tackle. The strong side defensive end lines up directly in front of the strong side guard. The object of the weak side defensive end against the run is to protect against reversals and counters. Otherwise on pass plays he goes after the quarterback. The strong side defensive end is to make sure the offensive guard in front of him does not push him inside and does not get released to block the linebacker.
Defensive tackles: The weak side defensive tackle lines up in front of the guard. The other defensive tackle essentially becomes a nose guard and lines up in front of the center. The main objective for the weak side tackle is the same as the strong side defensive end – to avoid being pinched inside or let the guard release to block the linebacker.
Linebackers: The jack linebacker lines up on the outside shoulder of the strong tight end and, like a defensive lineman, lines up on the line of scrimmage. He ensures nothing gets outside of him on the run. He can do multiple coverages on the pass or he can blitz. The charley linebacker will line up on the line of scrimmage and on the inside shoulder of the tight end, to cover the tight end or making it difficult for the tight end to release easily. The middle linebacker will line up about four to four and a half yards off the line of scrimmage and directly in front of the strong offensive tackle.
Safeties: The strong safety will line up four to four and a half yards off the line of scrimmage and will stand directly in front of the weak side tackle. The free safety will stand about ten to twelve yards away from the line of scrimmage and will stand directly in front of the weak side guard.
Cornerbacks: Corners will line up seven to eight yards off the line of scrimmage in front of their receivers in man-free coverage or they will play up on the line of scrimmage in bump and run coverage.