Miscast characters
I always felt like Riker was miscast on TNG- he was not a good actor, had two facial expressions I think and zero subtlety. On DS9 IMO Sisco and Kira were miscast- Sisco is just too quirky and Kira is too excited and happy to believe she's some battle-hardened warrior at 100 lbs. The doc also- he's a little too cute and silly.
Who did they get right? IMO Odo, all of the Ferengi (awesome!), Jadzia's OK, the Cardassians were well chosen. I get that it's essentially a soap opera set in space but a bit more space and less opera would have done us better IMO.