How significant would the difference be?
AFAIK, Titanium will generate Objective C, so unless their stuff is woefully inefficient, I wouldn't expect speed to be a major issue.
Are there other reasons to not use Titanium (or equivalent)?
Well, that depends on how you define "equivalent".
Personally, when I get into cross-platform apps, I expect that I will use PhoneGap. That's for one reason: standards.
With PhoneGap, you're writing HTML, CSS, and JavaScript, as if you were writing an HTML5 offline app. All PhoneGap does is turn that into an installable package (e.g., APK for Android) and give you opt-in proprietary APIs for getting to device-specific stuff. Their expectation is to simply fill in the "gap" between what HTML5 on mobile supports and what native apps on mobile supports. Heck, it's even in their name. :-)
As a result, what you are writing is the same sort of tech you would use for a Web-based app, and it may even get to share some of the client-side code. You can use whatever you like from mobile frameworks (e.g., Sencha Touch, jQuery Mobile). And, if someday app stores support HTML5 offline apps, you might even be able to drop PhoneGap altogether, if you're not heavily dependent upon the device integration features.
Titanium lets you write in JavaScript, but the standards compliance largely ends there. You're using proprietary APIs for everything, including the whole UI. Personally, I'd rather back a more popular horse -- HTML5 in this case, more so than PhoneGap specifically. If for no other reason, it'll be way easier to hire HTML5-savvy developers than Titanium-savvy developers.
Neither PhoneGap, nor Titanium, nor any of the plethora of other options (e.g., Rhodes, Flash/AIR) give you all of the device capabilities. These engines will vary in their extensibility -- I know that PhoneGap has a plugin model, that Flash/AIR is pretty much only what you get from Adobe, and I'm not sure about any others.
Titanium has one advantage: you get a near-native UI, instead of an HTML-based UI. (I say "near-native" because some of their widgets do not necessarily have native equivalents on all platforms, so they roll their own as needed) For some apps and some audiences, that alone may tilt things in Titanium's favor.