I don't see major problems.
Bike lanes take away parking spaces, but downtown is not residential in the sense that residents park their cars on the street in front of their houses. It's all folks who could easily use a parking ramp.
Taking Smithfield as an example. There's three lanes. One is bus going south, one is cars going north. Plus a parking lane. If the parking lane becomes bike lane nothing really changes. The same idea applies to other one-way streets. And not every street needs a bike lane. We just need a couple of cross-town bike lanes. Up and down would include Allies, Liberty, and Ft. Duquesne. Maybe Forbes and 7th(?), with are one-way/three-lane. Remember, not every street needs to be converted (as long as the rest are sharrowed, say).
Accommodating to other uses (bus, alleys, driveways) should just mean that the bike lane markings disappear for a bit or turn into dashes. Not a big deal.
My impression is that if you have at least three lanes to work with you're good. Downtown Pittsburgh is like that.
As an example, here's a street in Brooklyn:
One two-way lane for bikes, parking lane, one-way for cars, and even parking on the other side! (Given there's 4 lanes.)