I'm still using 3D rendering approaches but in an orthographic context, so I can still use models and skeleton animation to free me up from drawing sprites (which I'm not good at).
I saw a picture of Braid in the days before Jon Blow hired an artist and it made me realise that I can get the whole mechanics of a game in place using almost meaningless art before I worry about the visuals side.
So I've put some routines in to draw my skeleton as exported from the modelling package just with lines and dots and am going to just get the mechanics working using this debug drawing approach, safe in the knowledge that, in theory, I can replace the skeleton with a rigged model at any point in the future and all should just work.
So far you can walk, run and fall and it handles slopes correctly. Need to get jumping, edge grabbing and climbing sorted next.
There's a pretty interesting article on Gamasutra about how the artwork for Braid was developed. Worth a read I think.