Yep, good ergonomics and no sharp edges in the handle area is what makes my hand sing.
Also, handles that are built for purpose, while retaining ergonomics. What I mean:
1. camp knife: secure in a word. Single guard, flared butt for retention in chopping, and helps on pull stroke.
2. hunting knife: single guard, drop in the butt for draw stroke, small flare at butt ok, radiused spine, and if jimping is there on spine, it shouldn't be harsh. In fact, I'm not sure I really like or need jimping.
3. Kitchen knife: first, handle must be well above the bottom of the blade so you can chop veggies without hitting your knuckles. A flared rounded guard on the tang beats the feel of thin stock against your index finger. Drop at the butt.
4. Self defense knife: substantial index finger "guard", mild flare ok, drop at butt for sure, secure in a word. Add "stout, secure lock" if a folder, as to handles the topic, with lock recessed enough to not accidentally release it under stress.
5. working folder: strong lock. same as self defense but less of an issue on all traits. jimping on spine or between tang and stop pin on handle is fine if not harsh.
These guys come to mind as being good examples typically: RJ Martin, JW Smith, Terzuola's ATCF works for me, lots of the ABS guys get it right for working knives, Broadwell, Brend, anybody who makes a Loveless type drop point with any concessions to modernization, I like Maddogs grip except it needs a flared butt on the bigger knives, same for Allen Blade. Darrel Ralphs EDC does well for shape. Emerson Mach-I for a defense folder gets close, Commander is very good. BM 710 is a good all arounder for working piece, AFCK is good for what it is also, so is Spydie Wegner. A number of Dozier's knives have a simple elegance that is comfortable and work well.
Broadwell's LDC-107 still sticks out in my mind, so do RJ Martin's Oddessy, Trek, and an RJ in M2 that looks like a 7" Brend Model 2. JW Smith's recent tac folders are very nice.