Gene Roddenberry's concept of the warp field was that it was symmetrical and needed to be in open space. That's why the nacelles are not in direct line with the hull of the ship - it wouldn't be possible to create a stable warp field with bits of ship in the way!
You can see the same design concept in Klingon, Romulan, and Ferengi ships to name a few. This design was not universally followed by all Star Trek ships, but many or most of the ships in the original series and the Next Generation did follow this design principle.
Voyager can't go to warp until the nacelles have direct line of sight with each other. I can only imagine that the Defiant has a big, open space inside the ship for the warp field, which contributed to the ship being so cramped!
From An Exclusive Interview with Andrew Probert:
Tyler: Do you know the origin of what have become known as "Roddenberry's Rules of Starship Design" -- the idea that warp nacelles have to be in pairs, and things of that sort. I understand that there were a set of guidelines. Do you recall the origin of those?
Probert: Gene specified to me, in fact, that starship warp engines operate in pairs... only in pairs because they're codependent. If you had one warp engine, you'd probably go in a circle, I don't know... (laughs) So in the same breath he negated the three-engined dreadnoughts along with the single-engined destroyers, on the edict simply that, to achieve warp drive, you had to have codependent warp engine pairs. As far as the line-of-sight requirement, that was my edict, that, in order to be codependent, the warp engines had to "see" each other, totally. I'm taking about the power combs, not necessarily the Bussard collectors but the bulk of those combs have an energy path between them. And then for other starships, just like in World War II, where all the nations had fighter aircraft that all looked different -- you know, a cultural distinction between, say, a German aircraft and an American aircraft or a Japanese aircraft -- they all operated in the same way having the same basic components of wings, body, and engine, so I applied that thinking to the alien ships I designed as well, so the Ferengi ships, and Romulan Warbirds, have twin warp engines that have to see each other in order to operate. Even my shuttlecraft having a very shallow clearance, still see each other. That's why designs like the Romulan scout ship, where the engines cannot see each other, aren't consistent. There are also some cool Starfleet designs like the Nebula Class ships, but their warp engines cannot see each other. Even those runabouts ignore that ruling which messes up the continuity. Science fiction in particular NEEDS to be consistent. If you negate that,...it all falls apart.
(emphasis mine)