I think number one might be a bit too obvious.
From the link:
1) Key people start to leave. In every business, employees will come and go, and most people have heard the HR mantra that “everyone is replaceable.” But if founders or early hires that are in executive management begin to leave without a good reason, there’s probably trouble in start-up land. In January 2008, Thoof, a start-up competitor to Digg in the news voting space, went on the block and subsequently went under. An early warning sign? Alan Ren, co-founder, COO and CTO, left the company.
