There is some crazy finger gymnastics, I’ll admit, but it does help that the command key is meant to be hit with the thumb, making it sort of a chording system. Command with thumb, shift with pointer finger, and the middle or ring finger is free to hit ~.

Out of curiosity, have you looked at Monobjc, which is a Mono runtime that works on Mac OS? The other thing that might interest you is taking a look at Cocoa, if nothing else but for curiosity’s sake and looking at the design patterns there. The transition is easier than before, as on Leopard and Snow Leopard (but not iPhone), you can make Cocoa apps that have automatic garbage collection as opposed to retain/release pairings, and objective C 2.0 has some other niceties. A while back, dotnetaddictgave it a spin, and he’s produced a number of posts since then in a nice compare and contrast.