Kim,
I use PKSharpener as well and find the 3-stage sharpening technique works very well with RAW files which is what I shoot primarily. The plug-in's sharpening brushes and the flexibility to use luminance or high pass sharpening at different levels gives a tremendous amount of flexibility with different subject matter of different contrast ratios.

And I like the fact that you can sharpen the output for whatever device you're using whether it's my Epson 1800 or MPIX's photo output.

On the other hand, I've been testing CS3 and its implementation of Smart Sharpening is pretty good especially if you don't mind fading it out some at 200% view to remove the "grain".

I find that you have to use your own judgment about sharpening -- some subject matter demands a lot of it; some requires only judicious applications of it. Which is why I like PKSharpener because it gives you three levels of sharpening and lets you see what you're getting at each level.

As for upsizing, I seldom print larger than 8X10 and usually don't have to do any interpolation from my original files and, when I do, I find that PhotoShop's Bicubic Smooth does just fine. But I don't make large prints very often so I can't comment on how well it works for major resizing.

Jim