I skipped TG and DB on my main character who was not a theif or assasin (or a bard for that matter). I have started 2 new characters, but the luster has worn off the game (DLC, already!) and I don't know how far I'll end up taking those 2 new guys. I could use the TG & DB as de facto DLC, as I haven't done either, but neither of my two new guys is a thief or an assassin so perhaps the concept of those guilds/questlines just doesn't appeal to me as a real life person. I don' like not having seen all there is to see, but on the other hand, I'm not so sure I want to participate in either group.
I did the Thieves Guild right away, right out of Helgen, when I was new (and broke).
Doesn't make sense for an accomplished guy with money and homes to join them...
Then I did the Companions; then the Mages Guild.
At this point I settled the Civil War (doesn't matter which side) and it left my guy a stone-cold killer, and a little bit loopey too...
Basically a good-guy, but he had post-traumatic stress disorder.
Perfect candidate for the Dark Brotherhood, right?
You've just gotta role-play your guy into these scenarios - it's not really "you" after all, is it...