1. Is the large clearance between tire and fender necessary?

Only fitting by trial and error will determine if you will have sufficient clearance.

2. Larger tires = Lower RPM. . . . but are there any damaging repercussions if the OBC is NOT reprogrammed for the new diameter?

Not to the OBC. Your odometer will read under the actual. The speedometer won't be out as far, as it is optimistic to start, by design.

Apart from the OBC, you will have some negative effect of such a heavy tire. Consider the increased wear on suspension components, and inertial effects of the increased tire at that position on the rim, which will mean slower acceleration and braking.

3. Transfer case considerations - would it be prudent to find a tire combination for the set that starts with a SLIGHTLY larger diameter in the front? Thus the fronts could wear down to equal diameter . . . and then only approach a diameter disparity limit when the set of four is due for replacement . . .

No. Always try for matched. Don't expect that they are going to wear down evenly in any case.

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2007 X3 3.0si, 6 MT, Premium, White

Retired:
2008 535i, 6 MT, M Sport, Premium, Space Grey
2003 X5 3.0 Steptronic, Premium, Titanium Silver
2002 325xi 5 MT, Steel Grey
2004 Z4 3.0 Premium, Sport, SMG, Maldives Blue