Before using the Fitting module to automatically fit parameters, it is important to run the model in Simulator and perform some initial manual fitting.  There are a number of benefits to this:

1. It allows checking of obvious input errors (such as process temperature etc.) which cannot be detected in the Fitting module.  You cannot check a model the model in this level of detail within the Fitting module.  Opening in Simulator also allows run times for each simulation to be quantified and optimum solver settings to be identified (e.g. if run times are too slow).  Open and run each scenario in Simulator before fitting.
2. It enables checking consistency of units between your data profiles and the default units of the corresponding profiles calculated in Simulator.  In order for Fitting to work correctly, your data profiles must have the same units as Simulator.   The units in Simulator are determined by the units you have specified in the Excel model with the following priority: Scenarios sheet units override Process sheet units; if no units are specified chemical species units will be moles (standard model) or mol/L (if you have set up your model in concentrations).
3. The sensitivity of the simulator results to changes in the parameter values can be assessed.  This is important if either the fitting exercise has been set up correctly (e.g. trying to fit activation energies to a single isothermal data set) or changing the parameter value does not change the simulated results.  In the latter case it is often that the parameter is too small (or too large) so that changing it does not noticeably affect the simulation results (e.g. changing a rate constant from 1e-20 1/s to 1e-19 1/s will not have any great affect).  In order for the automated fitting module to work, the initial guesses for the selected parameters need to be in a region of sensitivity, otherwise the fitting algorithm will assume that it has reached a good fit (i.e. changing the parameters will not improve the fit).
4. Manual fitting of the model parameters in Simulator allows closer inspection of the quality of the data.  For example, if the data suggests more product is formed than substrate used, then there must be some inaccuracies with the data.  This will not be automatically detected in the Fitting module and would result in a poor fit.

The aim of manual fitting should be to generate a reasonable initial guess for the automated fitting routine to start from.  In order to do this it is necessary to find parameter values which show sensitivity.  It also discourages unrealistic fitting tasks (e.g. fitting 15 parameters to one data profile).  When fitting manually, include as much chemical knowledge as possible into the initial guess (e.g. if reaction 1 is very fast, give it a high rate constant, if you believe that reaction 2 is faster than reaction 3, this should be reflected in the initial parameter guess).  This will make automated fitting easier and quicker. 

Note that when building your model, you can set reactions with fast kinetics to be 'fixed', this will mean that the kinetics of those reactions will not be available for estimation in the Fitting window.