I can't seem to get any one of the .com domain that I want, mostly because of squatters. The .co domains seem to be available. How much of a disadvantage is it to not own the .com domain?
So, if the name/domain/brand is crucial to the success of the company (if it's a clothing line for example), then maybe it's worth spending a lot of time brainstorming until you find a .com that works.
But, if the core value-proposition of your product has little to do with the public-facing branding, then your time is probably best spent elsewhere, and you should just buy whatever domain is available ASAP and move on to other things.
However if your product is a mainly accessible via a mobile app then I would use the .co or other clean TLDs. For example, Vine is still using .co and it's a massive success.
For some tips on naming, see my Trello board of notes on naming and domains: https://trello.com/b/TekvQe5x/naming-and-domains
A marketing expert acquaintance recommends one-word names over the two-names approach you advocate there, though.
From your trello: "Even internationally, two English words is usually considered fine. This works for a number of sites, Facebook being one of the most notable examples" (I also thought of SnapChat, InstaGram, etc.)
However, the marketing expert wrote this advice to me "No future company is called (bad two-word names), they're called google, oracle, hulu or oculus. Go clean and easy to remember & pronounce""
I'd say best you can do is make your site https and responsive and make sure you have all relevant SEO data to increase its indexing performance.
Interestingly .biz and .co which were designed for businesses are heavily blacklisted.
But you're right, that was not the first intent.
You need .com