We regularly run 4 rods on our boat (we both have the 2-rod endorsement) and have been doing so since the endorsement was available. We have not tangled a single line so far, with the exception of some wildly swimming trout where we have had crossed lines, but not tangled while trolling. We do most of our trolling without downriggers.
As Joe mentioned, make slow, wide turns, and pay attention to the angle your line is from the rod to the water. If your lines are at more than a 30° - 40° angle to the rods you will be susceptible to tangles. You want to keep the lines more or less straight our from the rods. Hard to do when turning, but if you keep the line angles reasonable, you won't have as many problems. Another important element, if you fish both rods at the same depth, with essentially the same gear the odds are you will very likely experience tangles in a smaller boat. You need to separate the offerings by depth or amount of line out.
Try fishing off opposite sides with one rod forward and one aft, stagger depths, and make slow, easy turns. This will really help reduce your tangling issues.
I'm always amazed at the rigs I see on boats fishing the Great Lakes - rods and lines everywhere, and how they keep them from tangling seems nothing short of a miracle to me.
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