UEFA is the one with most variation.
Overall, I would probably go with CONMEBOL (with Brazil) as being the toughest. Enough really excellent teams to occupy the qualifying positions. Can't hide from anyone. Going on the road fricking sucks.
Both COMNEBOL and UEFA are far and away the most difficult but I think Europe is the toughest as evidenced simply by the sheer number of very solid teams that don't qualify many cycles (Russia, Belgium, Turkey, Sweden, Switzerland, Serbia etc).
I agree with how tough the road matches are in COMNEBOL but places like Serbia and Russia are no cake walk either.
I'd think we'd do very well to actually win a UEFA group once every 4 cycles:
To win a group we'd first need a lucky draw that avoids Spain, Germany, Italy, Holland in any cycle and hope we can beat Portugal, France, Belgium, England etc the 50% of the time we avoid those first four.
So, in 3/4 cycles we'd be trying to finish 2nd and then have to win a playoff knockout against another team pretty close to our level.
I think in UEFA we'd probably make 2 of every 5 World Cups.