4. Love it or hate it, Obamacare will be an IPO moneymaker.
It seems everyone has had something bad to say about the Affordable Care Act. But where some Republicans see socialism, venture capitalists see a business opportunity. New York City-based Psilos Group Managers has raised more than $580 million in bets placed on the health-care economy.
Obamacare needs some tweaking, said Steve Krupa, a managing member at Psilos, but one of its core concepts is hugely important from a business perspective: "The most important part is a guaranteed insurance market in a certain price corridor," Krupa said. "That changes the game in health care completely."
Psilos invests in technology to improve care in hospitals and reduce insurance company costs. One investment is Patient Safe Solutions, a San Diego-based company that is taking on a 20 percent error rate in prescriptions by giving nurses a mobile device to scan prescriptions and verify the right patient is getting the right dose.
(Read more: An outrageous price for WhatsApp? Now hold on ...)
5. Yes, you should follow the herd.
Sure, a lot of money is flowing to cloud and mobile, but "the herd" is not the only reason to dismiss these tech niches. "Mobile is a fundamental game-changer," said Venky Ganesan, a managing director at Menlo Ventures in Menlo Park, Calif. "It's like going from radio to TV or going from rail to air. It's going to fundamentally reshape every aspect of our life (and economy)."
Ganesan understands Facebook's willingness to pay up for WhatsApp. "Getting a sticky mobile app (and mobile messaging is the most sticky app of them all) is equivalent to buying one of the few keys to the mobile kingdom."
Ashton Newhall of Owings Mills, Md.-based Greenspring Associates feels the same way about cloud computing, which provides computing power and storage on demand. It's been a hot area for investing in recent years." I worry more about pricing than overcrowding," Newhall said. "There are a lot of different verticals that are yet to go to the cloud. There needs to be infrastructure improvements, the plumbing."
(Read more: The right way to get ahead in the cloud IPOs)
6. Don't overlook the case for fundamentals amid all the buzz.
Even while VCs have to chase the hot start-ups, they look for solid fundamentals. And unlike the roaring years preceding recent bubbles, many investors prefer companies that turn a profit. Hartenbaum cited Zulily, the e-commerce site for infant clothes that had a $2.6 billion IPO last November.
Started by veterans of Blue Nile, a high-end jewelry site, the business was profitable from the start and could do $1 billion in business this year. The key is that the company can deliver personalized post-sale pitches to customers who will keep buying as their children grow, Hartenbaum said. "They are selling kids clothes to Mom. As soon as Mom makes the purchase, they know that Mom has a six-month-old boy. It's not a one-off thing."
Despite successes like Zulily, the venture capitalist said e-commerce as a niche has not been a winner—most sites have failed to make money. Another area that has failed to produce a winner is mobile payments, despite the obvious need. These missed opportunities are a reminder that no matter how much data you collect and regardless of the level of buzz, investing will always be a gamble. "We have general ideas, but there are always surprises," Claremont Creek's Straub said.
—By Joel Dreyfuss, Special to CNBC.com