A lot of websites are first designed in Photoshop and then implemented in the browser. There is nothing wrong with this approach, because it helps to create something unique. But it becomes a problem when the user can clearly say that this was a Photoshop site (design needs to be transparent). Such sites look flat, artificial and flyer-like. Their interaction mechanisms are non-obvious, and interaction is given only a second-thought once the site gets in the development phase. During the design, the behavior of individual pages remains unclear, but this doesn't mean that it shouldn't be considered. We must be aware of what will happen during development and actual use that would be against our initial design intentions. Moreover, we need to consider whether the design will remain consistent in case we decide to vary element positions across multiple pages.
The purpose of creating Photoshop layouts isn't to make them pixel-perfect, but to clarify intent among stakeholders. Layouts can't be a complete replacement or equivalent for the client-server communication the user will be exposed to. Neither designing in Photoshop nor designing in the browser give us the ultimate answer to our needs. How well we can combine their advantages is what makes websites functional and beautiful. Going to any extreme hurts the design as it has proven to be not only a combination of different tools and technologies, but also influences, approaches and thought trains.
We can think of a layout as a map of directions. Going in any direction is bound with the opportunity costs of being unable to go in another one. Part of what makes journeys interesting is that they leave room for exploration. When we mask the entry points to these directions, we effectively hide the experience beneath.
The ease with which Photoshop layouts can be created and copied means that more sites become alike. Just because we have few primary and secondary colors doesn't mean that every site should have same-color UI elements. This effectively washes out good design and puts it aside. There is a growing trend of ineffective combination of design elements, simply because their number has skyrocketed. It becomes harder to keep an overview of what is available and in what context its use will be justified. The creation of packages of UI components means that we are more aware of inconsistencies now, but we still have the trouble to create a unique layout with only a single package. A designer can specialize now in inspecting the compatibility of a number of different elements the same way a developer specializes in using frameworks. Photoshop can help if we use it to critically evaluate the harmony of the whole or be harmful if we use it to integrate the first design element we discover in order to impress a client. With it, we can approximate the visual design of our site, but not the design. Using Photoshop rarely makes a designer in the absence of a highly developed sense for the details.
We don't need to make things artificial. Design involves creating something novel, not reusing old things that are very likely to create the next commodity. What was design yesterday is just a product today. The today's design is something noone else has done before, so not every website is an example of web design. The flat mask needs to be replaced with something that has contours, volume and shadow, something that would one day react to speech, smiles and sneezing.