I did the Glasgow to Dumfries section at the end of last summer as part of a tour. The bit out of Glasgow was mixed, standard Sustrans crappy circuitous and stop-start route. I was doing that part at night so once out the centre just jumped on a bus lane and rejoined the route at Paisley canal.
The route to Ayr was really enjoyable, out of Ayr you are on a busy road for a mile and then back in the countryside and quiet roads. I didnt do the alternate section through Galloway Forest but even the primary route through Newton-Stewart was enjoyable. If you are on a road bike the section out of Gatehouse of Fleet is pretty rough, but the alternative is the busy A75 so worth tackling, even slowly (unless its midge season).
The section from Penrith to Sunderland is the C2C, so not too difficult to follow. I think you could do Glasgow-Sunderland in 3 days if you were happy to do long days.