Mergers gone awry had once scared relatively cash-strapped companies away from big, risky deals, Calacanis said. But now mega-technology brands like Apple, Google and Facebook are sitting on big cash piles, watching as other large buyouts, like YouTube and Instagram, have proven fruitful.
"This DFIU strategy that a lot of large M&A companies have adopted — which is the 'don't frack it up' strategy — is actually working," Calacanis said. "M&A used to be you fire the founders, you take over the company and you probably mess it up ... M&A is actually working now."
That change in the environment has ushered in "massive activity" like Wal-Mart's agreement to buy e-commerce start-up Jet.com, Calacanis said, after Unilever's deal with Dollar Shave Club, Verizon's deal with Yahoo and Facebook's deal with Oculus.
"In Jet's case, it was a very nascent business," Calacanis said. "To get offered $3 billion for something that's only a couple of years old and really didn't have a ton of traction, that's one of the reasons why founders will sell. It takes out all they risk, they get a huge pay day and that's probably what we saw in this case."
Calacanis differentiated between "good" and "great" companies — those that are aggressively pursued but may not want to sell, versus companies that are not doing as well at the moment but their teams could do well inside other companies.
Calacanis, who said he did not speak with the founders, identified Netflix, Uber, Tesla, Snapchat, Airbnb and Slack as the "most desirable" takeover targets. Jawbone, Instacart, Twitter, Zenefits and Dropbox might be willing to be sold, Calacanis speculated.
CNBC reached out to those companies for comment.
"Timing is a key part of all this," Calacanis said. "If you look at a company like Dropbox, it was a fantastic company, printing money, and a lot of people invested at very high valuations. But of course, then Apple figured out the cloud, and Google and Microsoft figured it out even before Apple. So who's left? Who needs to buy them? I don't think there's somebody that needs to buy them."