I had an OG Droid for a year or so before I got my Thunderbolt. It really is similar to a Nexus phone, at least in regards to the experience. Compared to most of today's Android-powered phones, it had almost no additions to Android itself. The only real add-ons that made an appearance were apps pre-installed by Moto/Verizon (mainly Verizon, as always).
I was hesitant to make the jump to a device running a skinned version of Android, or more specifically, HTC's Sense UI. Long story short, while I very much enjoy vanilla Android, I've really become a fan of Sense.
Because of my great experience with Sense so far, I'm torn right down the middle between two upcoming phones -- the Nexus Prime, and the HTC Vigor (official names pending for each, of course).
I'm of the opinion that Sense definitely will not 'interfere' with your ability to perform daily routines, but it will take a little getting used to. It did for me, but then I really started to get accustomed to it.
I am, however, against Blur. Blur does nothing for me (read: for me) in terms of aesthetics or important functionality. Compared to Sense, Blur has always seemed sluggish when I've used phones running it.
Just my $0.02.