As far as a building, most Clevelanders would nominate the Justice Center courts tower - the beige beast that's front and center. In addition to being just an ugly and unappealing tower, there are three mid-rise buildings (jails, police HQ) that occupy the rest of the block. There's currently debate about rehab versus demo but who knows if that will happen in my lifetime
When it was built, the Justice Center complex was also a neighborhood killer as many of the buildings in the adjacent Warehouse District were demolished in anticipation of the need for parking. Fortunately the largest lot is now the site of the new Sherwin Williams world headquarters complex.
Although they're underutilized, the Malls that compose the large grassy space enclosed by the iconic Group Plan building could also be considered skyline killers, though I would never want to see high-rises built there. You can also see the Justice Center complex in the lower left.