It depends on the situation. In any 109 with a MG151 20mm cannon, I fire it at the same time as the machine guns because their ballistics are not too different. With the 30mm gun, I sometimes fire it independently when I have a good clear shot. On the other hand, I will fire the 30mm with the machine guns for a snap shot simply to increase my chances of scoring a hit. There's few things more frustrating for a K-4 pilot than to watch the enemy fly between the shells of a 30mm burst unscathed. in the K-4 I have shot down numerous aircraft with only the machine guns. You have to get a good long tracking shot, but if you hit a critical place, like a wing-tip, those 13mm guns can do some damage. I don't fly the G-2 or F-4 very much, but I spray the 7mm guns like crazy simply because there's so much ammo and it's extra weight if you don't use it.
Something should be said about using the machine guns to line up a shot with the 30mm cannon. We frequently hear that this should never be done because of ballistics issues, but that is only true at longer distances. At very close ranges and in the heat of a twisting fight, I frequently use the machine guns in the K-4 to set up a 30mm burst simply to get an idea of where my shells will go. This is especially helpful when you do not have the horizon in view because the lack of orientation can make predicting shell trajectory very difficult, e.g. when your noise is pointing nearly straight up but you're using a lot of rudder.