There are tons of issues with engine design and packaging. One wives' tale I'd like to get out of the way first, though, is "torque." Twins make about the same torque as an inline-4, they just stop making power sooner so without that huge rush at the top they
feel torqueyer... torquier... whatever.
Check the charts between the RC-51 and 999 vs. GSX-R1000 and ZX-10R. Having a much narrower operating band it's easier to tune out the valleys in the torque so twins usually don't have as much of a hit at 4k rpm like the i-4s do.
Another is that the vibrations are at a lower frequency. Both I-4s and V-2s have perfect primary balance and a secondary imbalance. The only time there's a difference in the frequency is in the 4-6,000 rpm band where the i-4 is making power and the V-2 is making shrapnel. I think the magnitude of the imbalance is less with a twin than a 4, but I don't know that as fact. The direction is slightly different but a secondary imbalance is defined as twice engine speed so there's no difference in frequency over the same rpm.
Twins are way thinner, but they're also a lot longer. This limits swingarm length and handling, and rider comfort. Compacting the twin to 75º or 60º requires a power-sapping and heavy system of counterbalancers. Compacting it more to, say, 45º makes it an unbearable lump with, honestly, no good qualities as an engine (its qualities as a replacement for an off-balance washing machine or paint shaker should be obvious). Twins also require twice as many head castings and twice as many cams. They're smaller and simpler castings, but I'm not sure if it's enough to make up for being twice as many, so I think cost is a toss-up. Also, the space taken up by two heads exacerbates the packaging problems.
V-4s have the good qualities of both engines, with the bad qualities of both engines. Narrower but longer, more power but more of the expensive components. They're better balanced, though, hence their popularity in MotoGP. Also, V-4s (and twins for that matter) can't get as much advantage from a "stacked" gearbox like what all the new sport bikes have.
IMO the best design for a street bike is the I-3 that Triumph uses. They get about the same fuel economy as I-4s, good top end with a smooth torque curve,
perfect primary
and secondary balance, and they're more compact than either other design. They only down side is that they need a counterbalancer to cure crankshaft wobble.
Here is one of my favorite web sites ever. The 180º twin has the same balance as an I-4, and the 90º twin is pretty obvious. Also, it shows a 60º twin so you can compare that to the 90 twin knowing that the further ou go from 90º, the worse the balance is.