I don't know if this is possible or not. Well, I know it's possible - but is it possible while still being good game design?
There's the 'side with the Sabbat' thing in Clan Quest that lets you avoid hallowbrook, and you can follow Bertram to avoid the warrens in CE (I think it's CE). If you have obfuscate and blood packs you don't have to fight anyone in Ventrue Towers except bomberman and the sheriff (ok, two elevator guards) - I'm sure you can sneak past a lot of it too and feed on the lone security guards as you go. You can sneak/obfuscate through most of Leopold, though you have to kill everyone at the bottom if you want a chance at saving the professor. If you run fast and know which way to go you can probably jump through a lot of Ming's temple, come to think of it (I'm usually in a 'kill 'em all, let God sort 'em out' mood by that point - they've got swords; I've got a Steyr Aug and super shotgun). Come to think of it, the Mandarin's whole 'torture chamber' gauntlet is a joke if you've got a shotgun and some ammo: The Mandarin seems like a smart guy, wouldn't he make you leave your weapons outside before you went through?
But if you do all that, you're pretty much bypassing entire chapters of the game. There's a point where you may as well just jump to the ending if you're going to skip everything in between. To give a contrast for what I'm saying: you can go through the beach house - yes, that 'quest' in the very beginning of the game - using 'social combat', but you still have to go through it, and work at it a bit. You don't just get to skip the whole zone.
Part of it is level 5 obfuscate is overpowered (IMHO) - pretty much the world is your playground once you have that. I can open and close doors with no one noticing. Hell, I can put a sword through someone's chest and the person he's talking to doesn't notice half the time (bush hook animations are even funnier).
The other piece though is the game seems to follow (whether by design or necessity in a rush to ship) a pattern of social/unarmed combat in Santa Monica, to some social/more melee combat Downtown, to still a bit of social, melee for the cemetery zombies [you certainly don't want to use 'Jaime Sue' - even if you found a spot where you could watch both gates you'd run out of ammo long before five minutes was up], take your pick for the walking head things (10 lockpicking gets you past a good bit of it - missing one pretty good 'story' dialog) in Hollywood. Chinatown is all about guns, baby. Yes, you have the awesome quests of talking to a couple of old guys, meeting a fat guy in a locker room, and walking across the street (literally) to get eyeballs out of a freezer. But the solution to any Tong problem is something with a large caliber. I already mentioned guns vs. the Mandarin. Hallowbrook and Leopold are both designed to be gun runs: Hallowbrook especially.
I don't know the answer to this one. I'm not sure the game gives you enough to work with to really let you put in other options, but it would be nice if there were some. Maybe alternate routes through sewers - reuse the existing maps - where melee would be more effective. Or maybe being able to sneak to humans you could persuade to open doors or otherwise let you continue.
I do know that I end a lot of my playthroughs right around the warrens because I know how the rest has to play out. Look Adrian! I'm Rambo,yo! with fangs. And I don't mean generally - to test my 'Heather' mod, I had to start at the lift outside the Hallowbrook and play to the elevator shaft every time I wanted to test a little change. The AI is so fixed I memorized exactly where to run, exactly how many shots it took and where to fire, and when to switch to a different gun for the whole route. If it has to be a gun run, at least let it be a good one...
At first I thought it may have been the mods I make to my personal games, but when CE Final came out I made a point of modifying nothing - the only real changes to my playstyle were carrying around a few more blood packs and making sure I was full on ammo with a backup gun (and I didn't have to worry about enemy guns as much). I'm probably rambling so I'll stop know. Hopefully there's a suggestion in there somewhere you can use.