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I'd assume that you'd be able to open the most squares by opening those that are completely disconnected from all other squares. That is, make a checkered pattern where there is at least one border of unopened squares around every opened one. (Except for 3's on the corners, 5's on the edges, and 8's anywhere in between, of course.)

Edit: Ah, this doesn't work, because of "You are still expected to select one of the adjacent cells." Clever.

Lines get you a lot more tiles on average it seems, but are extremely tricky to start playing. A cluster is more likely to force you to start thinking in 2 or 3 clicks, but is dramatically easier to start clearing a workable area, since the sides are not as entangled as they are in a line.

I've found it easier to hug the corners when possible, since it reduces the surface area in which you have to look for overlaps that might generate safe squares. In general, the game is easier when there are fewer places in the border.

No math proof, but I'd favor a cluster strategy as being faster to force a (partial) solution to existing clues.