Yes, they are very different. As mentioned, I have owned two twins, plus a four and the current flat-six.
Twins have gobs of torque that "shove" forward...the flat 6 has a lot of torque too, but it is distributed in a more linear way through the RPM range.
I like twin torque, as I am in no hurry. However, since having the flat 6, I do appreciate the hard pull of horsepower to go along with that aforementioned torque.
A question for you... the GW is an easy to maintain bike...oil changes, rear tire are a piece of cake.
How easy is it to remove the rear tire on the Venture?