RoutePrefix vs Route

For an authoritative source, here are the descriptions from MSDN (emphasis mine).

RouteAttribute

Place on a controller or action to expose it directly via a route. When placed on a controller, it applies to actions that do not have any System.Web.Mvc.RouteAttribute’s on them.

RoutePrefixAttribute

Annotates a controller with a route prefix that applies to all actions within the controller.

As you can see, the description for Route mentions exposing the action(s), but RoutePrefix does not.

Route prefixes are associated with routes by design in attribute routing.

It is used to set a common prefix for an entire controller.

If you read the release notes that introduced the feature you may get a better understanding of the subject.

ASP.NET Web API 2

Attribute routing

ASP.NET Web API now supports attribute routing, thanks to a contribution by Tim McCall. With attribute routing you can specify your Web API routes by annotating your actions and controllers like this:

[RoutePrefix("orders")] 
public class OrdersController : ApiController 
{ 
    [Route("{id}")] 
    public Order Get(int id) { } 
    [Route("{id}/approve")] 
    public Order Approve(int id) { } 
} 

Attribute routing gives you more control over the URIs in your web API. For example, you can easily define a resource hierarchy using a single API controller:

public class MoviesController : ApiController 
{ 
    [Route("movies")] 
    public IEnumerable<Movie> Get() { } 
    [Route("actors/{actorId}/movies")] 
    public IEnumerable<Movie> GetByActor(int actorId) { } 
    [Route("directors/{directorId}/movies")] 
    public IEnumerable<Movie> GetByDirector(int directorId) { } 
} 

What's New in ASP.NET Web API 2.1

What's New in ASP.NET Web API 2.2

A really good article on the subject

ASP.NET 5 Deep Dive: Routing

While no expert on the subject, here is my understanding of how this works.

With attribute routing the framework inspects the route attribute on the actions of a controller in order to create route entries to add to the route table. So as long as you are using attribute routing you are going to be using the [RouteAttribute]. Without this attribute the action will default back to convention-based routing. The RoutePrefixAttribute is an extensibility point that allows you more control of how you define your routes/Urls. The release notes say as much.

Other than my understanding and the last link provided, everything else was quoted from MS documentation.