If the National Popular Vote were to come to pass, we would need to standardize voting procedures across the nation - which may not be a bad thing, but I am not sure I trust Republicans with protecting voting rights in the country - now or in the future.
While NPV only affects the race for President, it also has an effect on every race down the ballot. Quickly, here are a few problems I see that could lead to worse outcomes for our candidates, recognizing that the ease of voting makes it more likely for people to vote.
1) Ballot Access - NPV would count all votes for President. Currently, in some states there might be a Green Party candidate that takes away votes from the Democrat. If California is one of those states, whomever the Democratic Party nominee would be would lose a large number of votes to the Republican, especially if a prominent third-party candidate did not make the ballot in California. Perhaps this is an unlikely example, but if we want a true popular vote for President, we need to make sure that every State has the same ballot for President.
2) Voter Registration - North Dakota has no voter registration requirement. Several States allow for same-day registration. Other States like Virginia have lifetime bans on felons voting; a couple State allow convicted felons to vote. If we want to have a true popular vote for President, we need to have equal access to the ballot.
3) Election Day - Oregon and Washington have vote-by-mail, California allows for permanent absentee voting. Indiana closes its polls at 6pm, New York closes its polls at 9pm. Again, we need to ensure that everyone's vote is equal, both in theory and in practice.
Thus, if we have a true popular vote for President, we will need to federalize our election processes and procedures. This can be a good thing, but I have doubts that our elected officials (of both parties [see Rhode Island Democrats and Voter ID] [but Republicans would be worse]) would enact election laws that are truly open and allow for maximum participation. Vote by Mail - gone; Same Day Registration - gone.
I would start with a Constitutional Amendment protecting the right to vote and go from there.