Well, since all of the 3.5's were low-grille, at least you won't have any engine/hood clearance issues

You'd definitely need someone (or need to be someone) who knows what they're doing. I had a 3.5 and I agree with you that it's a great engine. But the Bosch EFI is one thing that springs to mind right away. The Jetronic and its associated throttle system (and ignition) are all different from the mechanical injection in the 280SE.

Obviously the engine mounts are different, but I heard that they can be retrofitted (maybe with a donor subframe?). The power-steering unit is also an issue--clearances around the V8 exhaust manifolds etc--have I turned you off of it yet?

You'd also have to address transmission and rear-end gear ratio issues. The diff from a W108/W109 is supposedly an easy transplant FWIW. V8 power might be an issue for the 280 diff even if the gearing were appropriate.

Finally, of course, there is the matter of value, in that upon resale people usually pay more for original equipment, but that's your business. I'd honestly be inclined to find another 6 or rebuild the one you have. But I certainly understand the temptation to upgrade, especially if it's cheaper (since rebuilds aren't cheap).

I'm no expert on this, so if anyone else knows more or better, jump in!