As stated previously there are a few different factors, such as the location of the start up and the origin of the customers/visitors, if they are confied to a country or wider region a region specific TLD is not a bad choice, but for global or other markets .com is advisable.
Your choice for domain extension should be based on the niche of your website. It is better to have nich domains instead of generic domains. Furthermore, most of the names are already taken in dot com or other popular extension such as dot net dot info etc. However, on new extension the domain name of your choice can be still avauiable. For example I wanted a domain for a forum. sadly when I searched for MyLifeSucks dot com it was already taken, I settled with dot xyz.
The most appropriate domain extension really depends on what your website and respectively business will be related to. â€˜'.com'' is usually a great choice, especially if you want to develop your business globally. â€˜'. us'' or â€˜'.eu'' are great extensions if you want to focus more on the American or European market. I think it's better to pay more attention to the domain name itself, and choose a really good one, following the guidelines. As you probably know, it should be easy to remember and type. If you want it to be brand-related, you may purchase also other domain extensions, or variations of your domain name, so competitors can't take advantage of them.