The bootstrapping and orphan block issues are very interesting.  Bootstrapping will be slower.  Not sure if there is a way around that.  Orphans I think could be offset by having a higher number of nodes.  If you only have a few hundred nodes then the difficulty will stay very low and orphans will be a common problem.  I can see this with some altcoins even on Script, such as "SXC" and "WDC".  But, what happens if you have 15,000 nodes (such as Bitcoin)?  My hope is that the number of hashers out there will drive up the difficulty enough to keep the orphan count down.  Of course, this depends on fast network propagation.  I'm not sure if the Bitcoin software currently does network structure balancing to keep the path between all nodes the shortest possible but something like that may be needed to communicate out new blocks as quickly as possible to reduce the number of orphans being generated.