For me the toughest so far have been Blue Valley long here in KC and Mont Du Lac outside Duluth and for me toughest means most physically demanding. There are tougher courses as far as what shots you need or how technical a course is, but that's skill set dependant type tough not physically demanding tough.
Blue Valley kicks my rectum on the regular b/c I'm out there at least once a month. Length and elevation conspire to break the will of mortals out there. I usually play the front 10, which takes you back to the parking lot and is tougher than most other 18's around. Occasionally I'll play through 16, and leave the 2 1000 footers across the road alone. But it's only when I'm really hating myself or just have too much time to kill that I attempt all 18. Even my dog gives up after 10. She'll follow me reluctantly through 16, but after that she'll usually just wait at the car.
Mont du Lac had been hit by big floods when we went up there last year. Huge muddy gorges were carved out where you can tell there used to be a ski run, which is what it is in the winter. Navigation was darn near impossible, b/c of the damage by floods, holes having been moved b/c of said floods but not marked in any way or on any map, and the extreme elevation. Multiple top of the world type shots were fun, but all we could do that day was get up and down that course, get a beer and go to bed.