The walk is a little bit long, but definitely reasonable and it sounds like you are very familiar with urban walking, so based on that I think it's a walk you'd definitely be comfortable doing.
The area all around there is relatively safe. The only area I think I would avoid is Averil Ave, Pearl St, Meig St Square. But even on those roads, I don't think you'd have any issues. Looking at the crime maps it is a low crime area overall. As mentioned earlier, the Clinton Ave. S over to Monroe is very ethnic. I think your plans for walking over to the South Wedge makes sense. Are you staying over in the East Ave. area or downtown? And what route(s) were you preferring do you think? I could give some ideas on if it is a good route to take if you'd like too. Were you planning on going through the Park Ave area to get over there or up East Ave. to Alexander St?
The bus shouldn't be an issue too. On holidays it runs on Sunday Schedules. A bus goes every hour from South Ave/Gregory from 5:45 in the morning until 12:45 in the evening. If you are on East Ave, you can catch a bus downtown and then a connecting bus over to East Ave. from the bus station, unless you were looking to walk. Which is actually a nice and easy walk too.
you can plan your trip here:
Maps & Schedules
Where's My Bus? - Schedule