Here is my rundown:
MS Mappoint is more of a mapping program as compared to navigation app. I think its possible to build a decent navigation application out of it, but IMHO you're doing the job that MS should have done. Too much work involved. Besides you cant do 3D views.
Destinator - Main problem with it is the fact that it's designed for PDA's. Otherwise it has some nice features, though it reminds of good old windows 95/dos days with its menu's.
Delorme Streets - Havent tried.
Copilot - Expensive. Seems to be one of the best 'out of the package' deals. All the little quirks that annoy people in other apps seem to be fixed in copilot. But personally havent tried it, so cant say for sure.
Routis - Personal fav. POI database is not the best, but functionality wise its exactly what I'm looking for. It's lightweight, does exactly what it should do without any unnecessary routines. Great algorithms for recalculating routes, good maps. Not overpriced.