RouteBuddy is a very "Mac-like" GPS application for the Mac, and I have been able to successfully create waypoints and routes and upload them to my Garmin devices (Nuvi 660 and Oregon 400t, neither of which are "officially" supported, but both of which work with the device).
In 2 days of use, I've found it much nicer to use than Garmin's Bobcat software, which seems _so_ focused on showing my waypoints for the local gas stations and McDonald's. What I want, really, is to put in some waypoints for places I want to visit, or to hike to. And RouteBuddy makes that fairly straightforward... though the lack of any Topo maps for it is a bit limiting.
It's faster than Bobcat as well, for me.
I have had a couple crashes with the app, mostly when moving around and scrolling in/out. One of the big pains with this, that I've found, is that if you find and "save" a bunch of waypoints, but then RouteBuddy crashes, you lose everything you've done since the last time you quit the application. That IMO is _not_ nice... stuff should be written out instantly to avoid this. I don't want to have to trawl through and do everything twice.
Also, the map info they use, while good, has some inaccuracies. I mapped my parents house in Scottsdale, AZ and it came back with a City address of "Deer Valley." Though it put the house in the right location! This is not directly a RB problem, but because it's the maps they use, it certainly affects them. This is with the latest (2008-04) maps as well.
So in the end, it's $150-$170 for an application plus US or North America maps compared to what Garmin is offering for free. Worth it? Right now it seems like it has some legs, but let's see it get some more in terms of features and stability, and quick.